Exercise performance depends on both physiological abilities (e.g., muscle strength) and behavioral characteristics (e.g., motivati on). We tested the hypothesis that evoluti on of in creased aerobic exercise performa...Exercise performance depends on both physiological abilities (e.g., muscle strength) and behavioral characteristics (e.g., motivati on). We tested the hypothesis that evoluti on of in creased aerobic exercise performanee can be facilitated by evolution of neuropsychological mechanisms responsible for motivation to undertake physical activity. We used a unique model system: lines of bank voles Myodes glareolus selected for high swim-induced aerobic metabolism ("aerobic" A lines). In gen eration 21, voles from the 4 A lines achieved a 57% higher /y voluntary maximum" swiminduced aerobic metabolism (V02swim) than voles from 4 unselected,"control" C lines. In C lines, V02swim was 9% lower than the maximum forced-exercise aerobic metabolism (VO2run;P= 0.007), while in A lines it was even higher than VO2run, although not significantly (4%, P=0.15). Thus, we hypothesized that selection changed both the aerobic capacity and the neuronal mechanisms behi nd motivation to un dertake activity. We investigated the influe nee of reuptake in hibitors of dopamine (DARI), serotonin (SSRI), and norepinephrine (NERI) on VOaSwim. The drugs decreased V02swim both in C and A lines (% decrease compared with saline: DARI 8%, P< 0.001;SSRI 6%, P< 0.001;NERI 8%, P< 0.001), but the proportional response differed between selection directions only for NERI (stronger effect in C lines: P= 0.008) and the difference was marginally non-significant for SSRI (P= 0.07) and DARI (P= 0.06). Thus, the results suggest that all the 3 monoamines are involved in signaling pathways controlling the motivation to be active and that norepinephrine could have played a role in the evolution of increased aerobic exercise performance in our animal model.展开更多
The aim of this study was to determine the time course of changes in extracellular fluid (ECF) concentrations of purines, amino acids, monoamines, and their metabolites in the striatum of rats during ischemia and repe...The aim of this study was to determine the time course of changes in extracellular fluid (ECF) concentrations of purines, amino acids, monoamines, and their metabolites in the striatum of rats during ischemia and reperfusion, using intracerebral microdialysis as the sampling technique. In rats subjected to 20 min forebrain ischemia by four-vessel occlusion, the concentrations of adenosine (Ade), inosine (Ino) and hypoxanthine (Hyp) were found to rise markedly. These changes were accompanied by dramatically elevated levels of aspartate (Asp), glutamate (Glu), taurine (Tau), γ-aminobutyric acid (GABA), dopamine (DA) and norepinephrine (NE), all of which gradually returned to baseline following reperfusion. Concomitantly, the levels of metabolite 3, 4-dihydroxyphenylacetic acid (DOPAC) . homovanillic acid (HVA), 5-hydroxyindole-3-acetic acid (5-HIAA) and xanthine (Xan) decreased during ischemia and gradually recovered 60～ 90 min after reperfusion. It was concluded that during global brain ischemia, the ECF is flooded with both potentially harmful (e. g. Asp, Glu, DA) and protective (e. g. Tau, GABA, Ade) agents.展开更多
Monoamine neurotransmitters play an important role in the modulation of sensory, motor and autonomic functions in the spinal cord. Although traditionally it is believed that in mammalian spinal cord, monoamine neurotr...Monoamine neurotransmitters play an important role in the modulation of sensory, motor and autonomic functions in the spinal cord. Although traditionally it is believed that in mammalian spinal cord, monoamine neurotransmitters mainly originate from the brain, accumulating evidence indicates that especially when the spinal cord is injured, they can also be produced in the spinal cord. In this review, I will present evidence for a possible pathway for two-step synthesis of dopamine and serotonin in the spinal cord. Published data from different sources and unpublished data from my own ongoing projects indicate that monoenzymatic cells expressing aromatic L-amino acid decarboxylase（AADC）, tyrosine hydroxylase（TH） or tryptophan hydroxylase（TPH） are present in the spinal cord and that these TH and THP cells often lie in close proximity to AADC cells. Prompted by the above evidence, I hypothesize that dopamine and serotonin could be synthesized sequentially in two monoenzymatic cells in the spinal cord via a TH-AADC and a TPH-AADC cascade respectively. The monoamines synthesized through this pathway may compensate for lost neurotransmitters following spinal cord injury and also may play specific roles in the recovery of sensory, motor and autonomic functions.展开更多
Nowadays,presynaptic dopaminergic positron emission tomography,which assesses deficiencies in dopamine synthesis,storage,and transport,is widely utilized for early diagnosis and differential diagnosis of parkinsonism....Nowadays,presynaptic dopaminergic positron emission tomography,which assesses deficiencies in dopamine synthesis,storage,and transport,is widely utilized for early diagnosis and differential diagnosis of parkinsonism.This review provides a comprehensive summary of the latest developments in the application of presynaptic dopaminergic positron emission tomography imaging in disorders that manifest parkinsonism.We conducted a thorough literature search using reputable databases such as PubMed and Web of Science.Selection criteria involved identifying peer-reviewed articles published within the last 5 years,with emphasis on their relevance to clinical applications.The findings from these studies highlight that presynaptic dopaminergic positron emission tomography has demonstrated potential not only in diagnosing and differentiating various Parkinsonian conditions but also in assessing disease severity and predicting prognosis.Moreover,when employed in conjunction with other imaging modalities and advanced analytical methods,presynaptic dopaminergic positron emission tomography has been validated as a reliable in vivo biomarker.This validation extends to screening and exploring potential neuropathological mechanisms associated with dopaminergic depletion.In summary,the insights gained from interpreting these studies are crucial for enhancing the effectiveness of preclinical investigations and clinical trials,ultimately advancing toward the goals of neuroregeneration in parkinsonian disorders.展开更多
We develop here a simple wet chemistry to prepare covalent functionalized graphenes （FGs） through epoxide aminolysis espe- cially under alkaline aqueous condition. Remarkably, a series of typical monoamines, such as...We develop here a simple wet chemistry to prepare covalent functionalized graphenes （FGs） through epoxide aminolysis espe- cially under alkaline aqueous condition. Remarkably, a series of typical monoamines, such as industrial Huntsman Jeffamine M-2070 and M-2005 polymer with hydrophilic or hydrophobic polyetheramine chains, positively-charged 2-amino-N,N,N- trimethylpropanaminium, negatively-charged sulfanilic acid, even oligopeptide sequence, can be effectively grafted on the platelets of graphene oxide precursor with covalent functionalization and partially reduced features. This strategy provides the researchers a facile and convenient approach to design and synthesize solution processable, biocompatible and functionalized graphenes for the potent applications in electronic inks, drug carriers and biomedicines. Expansion of the current study is actively ongoing in our laboratory.展开更多
Objective: To study the mechanism of acupuncture in treating simple obesity. Methods: Central nerve push-pull perfusion and biochemical technique were used to observe the effect of acupuncture on the obese parameters,...Objective: To study the mechanism of acupuncture in treating simple obesity. Methods: Central nerve push-pull perfusion and biochemical technique were used to observe the effect of acupuncture on the obese parameters, changes of monoamine transmitters and activity of ATPase in the lateral hypothalamic area (LHA) of obese rats. Results: Noradrenaline (NA) level in LHA of obese rats was higher but serotonin (5-HT) level and ATPase activity were lower than those in normal rats. After acupuncture treatment, in the same time of reducing body weight, NA level in LHA of rats was reduced, and 5-HT level and ATPase activity in it were increased.(P<0.05 and P<0.01). Conclusion:The effective regulation on LHA of obese rats is possibly one of the key factors in anti-obesity effect of acupuncture.展开更多
In recent years, the importance of hypothalamic defence area (HDA) has attracted more and more attention. Many researchers demonstrated that HDA plays a very important role in cardiovascular and behavioral regulations...In recent years, the importance of hypothalamic defence area (HDA) has attracted more and more attention. Many researchers demonstrated that HDA plays a very important role in cardiovascular and behavioral regulations. However, so far release of central neurotransmitters during excitement of HDA is unknown. The present study showed that stimulation of HDA could increase the contents of monoamines and their metabolites, especially the latter, in the cerebrospinal fluid (CSF) of rabbits.展开更多
Type-B monoamine oxidase inhibitors,encompassing selegiline,rasagiline,and safinamide,are available to treat Parkinson's disease.These drugs ameliorate motor symptoms and improve motor fluctuation in the advanced ...Type-B monoamine oxidase inhibitors,encompassing selegiline,rasagiline,and safinamide,are available to treat Parkinson's disease.These drugs ameliorate motor symptoms and improve motor fluctuation in the advanced stages of the disease.There is also evidence suppo rting the benefit of type-B monoamine oxidase inhibitors on non-motor symptoms of Parkinson's disease,such as mood deflection,cognitive impairment,sleep disturbances,and fatigue.Preclinical studies indicate that type-B monoamine oxidase inhibitors hold a strong neuroprotective potential in Parkinson's disease and other neurodegenerative diseases for reducing oxidative stress and stimulating the production and release of neurotrophic factors,particularly glial cell line-derived neurotrophic factor,which suppo rt dopaminergic neurons.Besides,safinamide may interfere with neurodegenerative mechanisms,countera cting excessive glutamate overdrive in basal ganglia motor circuit and reducing death from excitotoxicity.Due to the dual mechanism of action,the new generation of type-B monoamine oxidase inhibitors,including safinamide,is gaining interest in other neurological pathologies,and many supporting preclinical studies are now available.The potential fields of application concern epilepsy,Duchenne muscular dystrophy,multiple scle rosis,and above all,ischemic brain injury.The purpose of this review is to investigate the preclinical and clinical pharmacology of selegiline,rasagiline,and safinamide in Parkinson's disease and beyond,focusing on possible future therapeutic applications.展开更多
Alzheimer's disease(AD)is gradually increasing in prevalence and the complexity of its pathogenesis has led to a lengthy process of developing therapeutic drugs with limited success.Faced with this challenge,we pr...Alzheimer's disease(AD)is gradually increasing in prevalence and the complexity of its pathogenesis has led to a lengthy process of developing therapeutic drugs with limited success.Faced with this challenge,we proposed using a state-of-the-art drug screening algorithm to identify potential therapeutic compounds for AD from traditional Chinese medicine formulas with strong empirical support.We developed four deep neural network(DNN)models for AD drugs screening at the disease and target levels.The AD model was trained with compounds labeled for AD activity to predict active compounds at the disease level,while the acetylcholinesterase(AChE),monoamine oxidase-A(MAO-A),and 5-hydroxytryptamine 6(5-HT6)models were trained for specific AD targets.All four models performed excellently and were used to identify potential AD agents in the Kaixinsan(KXS)formula.High-scoring compounds underwent experimental validation at the enzyme,cellular,and animal levels.Compounds like 2,4-di-tert-butylphenol and elemicin showed significant binding and inhibitory effects on AChE and MAO-A.Additionally,13 compounds,includingα-asarone,penetrated the blood-brain barrier(BBB),indicating potential brain target binding,and eight compounds enhanced microglialβ-amyloid phagocytosis,aiding in clearing AD pathological substances.Our results demonstrate the effectiveness of deep learning models in developing AD therapies and provide a strong platform for AD drug discovery.展开更多
Objective: In the manuscript titled Monoamine Oxidase-B Inhibitor Rasagiline Effects on Motor and Non-Motor Symptoms in Individuals with Parkinsons Disease: A Systematic Review and Meta-Analysis, the objective was to ...Objective: In the manuscript titled Monoamine Oxidase-B Inhibitor Rasagiline Effects on Motor and Non-Motor Symptoms in Individuals with Parkinsons Disease: A Systematic Review and Meta-Analysis, the objective was to conduct a systematic review with meta-analysis to investigate the effects that Rasagiline has on motor and non-motor symptoms in individuals with PD. Introduction: Rasagiline is a second-generation monoamine oxidase-B (MAO-B) inhibitor used both as monotherapy and adjunctive therapy for Parkinsons Disease (PD). Methods: A systematic literature search and meta-analysis were performed with randomized control trials that investigated the effects of Rasagiline on motor and non-motor symptoms in individuals with PD. The systematic search was conducted in PubMed, Cochrane, and EBSCO databases. Methodological quality was assessed using the Cochrane Grading Recommendations Assessment, Development and Evaluation approach. Results: Fourteen studies were included in our review. There were trivial to small and statistically significant improvements in motor symptoms for individuals with PD treated with Rasagiline compared to placebo. Non-motor symptoms showed no significant improvement with Rasagiline compared to placebo in five of six meta-analyses. Results were based on very low to moderate certainty of evidence. Conclusion: 1 mg/day Rasagiline significantly improved Parkinsonian motor symptoms in individuals with PD compared with placebo. For all outcomes, the 1 mg/day Rasagiline group was favored over the placebo group.展开更多
Monoamine oxidases(MAOs)are a class of flavin enzymes that are mainly present in the outer membrane of mitochondria and play a crucial role in maintaining the homeostasis of monoamine neurotransmitters in the central ...Monoamine oxidases(MAOs)are a class of flavin enzymes that are mainly present in the outer membrane of mitochondria and play a crucial role in maintaining the homeostasis of monoamine neurotransmitters in the central nervous system.Furthermore,expression of MAOs is associated with the functions of peripheral organs.Dysfunction of MAOs is relevant in a variety of diseases such as neurodegenerative diseases,heart failure,metabolic disor-ders,and cancers.Monoamine oxidases have two isoenzymes,namely,monoamine oxidase A(MAO-A)and monoamine oxidase B(MAO-B).Therefore,the development of reliable and specific methods to detect these two isoenzymes is of great significance for the in-depth understanding of their functions in biological systems,and for further promoting the clinical diag-nosis and treatment of MAO-related diseases.This review mainly focuses on the advances in small molecular probes for the specific imaging of MAO-A and MAO-B,including radiolabeled probes,fluorescent probes,and a 19F magnetic resonance imaging probe.In addition,applications of these probes for detecting MAO expression levels in cells,tissues,animal models,and patients are described.Finally,the challenges and perspectives of developing novel MAO imaging probes are also highlighted.展开更多
Abstract： In the presem study, we simultaneously quantified the levels of monoamine neurotransmitters （MANTs） and their metabolites （levodopa, norepinephrine, epinephrine, dopamine, 5-HT, 3,4-dihydroxyphenylacetic...Abstract： In the presem study, we simultaneously quantified the levels of monoamine neurotransmitters （MANTs） and their metabolites （levodopa, norepinephrine, epinephrine, dopamine, 5-HT, 3,4-dihydroxyphenylacetic acid, homovanillic acid and 5-hydroxyindole-3-acetic acid） in different brain subregions of rats using a newly developed simple, sensitive and selective high-performance liquid chromatography with fluorescence detection （HPLC-FLD） method. In this new HPLC-FLD method, analytes were directly extracted and separated without deriveatization step within 20 min. The FLD wavelength was set at 280 nm and 330 nm for excitation and emission, respectively. The analytes were separated on an Agilent Eclipse Plus Cls column （4.6 mm×150 mm, 5.0 μm） equipped with an Agilent XDB-C18 security guard column （4.6 mm×12.5 mm, 5.0 lam）, and the column temperature was maintained at 35 ℃. The mobile phase for elution was isocratic. The mobile phase consisted of citric acid buffer （50 mmol/L citric acid, 50 mmol/L sodium acetate, 0.5 mmol/L octane sulfonic acid sodium salt, 0.5 mmol/L Na2EDTA and 5 mmol/L triethylamine, pH 3.8） and methanol （90：10, v/v） at a flow rate of 1.0 mL/min. The detection limit （DL） was 0.9-23 nM for all the MANTs and their metabolites with a sample volume of 50 μL. The method was shown to be highly reproducible in terms of peak area （intraday, 0.08%-1.85% RSD, n = 5）. The simultaneous measurement of these MANTs and their metabolites improved our understanding of the neurochemistry in the central nervous system （CNS） in relation to different addictive drugs （methamphetamine, heroin and their mixture） in drug-addicted rat models.展开更多
Aggression is a common behavioral trait shared in many animals, including both vertebrates and invertebrates. However, the type and intensity of agonistic encounters and displays can vary widely both across and within...Aggression is a common behavioral trait shared in many animals, including both vertebrates and invertebrates. However, the type and intensity of agonistic encounters and displays can vary widely both across and within species, resulting in complicated or subjective interpretations that create difficulties in developing theoretical models that can be widely applied. The need to easily and objectively identify quantifiable behaviors and their associated morphologies becomes especially important when attempting to decipher the neurological mechanisms underlying this complex behavior. Monoamines, neuropeptides, and pheromones have been implicated as important neuromodulators for agonistic displays in both invertebrates and vertebrates. Ad- ditionally, recent breakthroughs in insect research have revealed exciting proximate mechanisms important in aggression that may be broadly relevant, due to the relatively high conservation of these neurochemical systems across animal taxa. In this review, we present the latest research demonstrating the importance of monoamines, neuropeptides, and pheromones as neuromodulators for aggression across a variety of insect species. Additionally, we describe the stalk-eyed fly as a model system for studying aggres- sion, which integrates physiological, morphological, and neurochemical approaches in exploring detailed mechanisms responsible for this common yet complex behavior. We conclude with our perspective on the most promising lines of future research aimed at understanding the proximate and ultimate mechanisms underlying aggressive behaviors .展开更多
The organization of the brain serotonergic system appears to have been highly conserved across the vertebrate subphylum. In fish as well as in other vertebrates, brain serotonin （5-HT）, mainly acts as a neuromodulat...The organization of the brain serotonergic system appears to have been highly conserved across the vertebrate subphylum. In fish as well as in other vertebrates, brain serotonin （5-HT）, mainly acts as a neuromodulator with complex effects on multiple functions. It is becoming increasingly clear that acute and chronic increase in brain 5-HT neurotransmission have very different effects. An acute 5-HT activation, which is seen in both winners and losers of agonistic interactions, could be related to a general arousal effect, whereas the chronic activation observed in subordinate fish is clearly linked to the behavioral inhibition displayed by these individuals. Fish displaying diver- gent stress coping styles （proactive vs. reactive） differ in 5-HT functions. In teleost fish, brain monoaminergic function is also related to life history traits.展开更多
Effects of acupuncture on the levels of neurotransmitters in the raphe nuclei were investigated in obeserats.It was found that the levels of tryptophan (Trp) and 5-hydroxyindoleacetic acid (5-HIAA) wereincreased,and 5...Effects of acupuncture on the levels of neurotransmitters in the raphe nuclei were investigated in obeserats.It was found that the levels of tryptophan (Trp) and 5-hydroxyindoleacetic acid (5-HIAA) wereincreased,and 5-hydroxytryptamine (5-HT) level and 5-HT/5-HIAA ratio decreased in the raphe nucleiof the obese group as compared with the normal group;and that acupuncture could produce weightreduction,increase the 5-HT level and 5-HT/5-HIAA ratio,and decrease the contents of Trp and5-HIAA,but did not change the levels of dopamine (DA) and noradrenaline (NA).It is indicated thatbenign regulative action of acupuncture on 5-HT and its metabolism in the raphe nuclei is possibly oneof the factors for reducing weight by acupuncture.展开更多
The aim of this study was to investigate the effect of 30 min forebrain ischemia, followed by 120 min reperfusion on extracellular fluid (ECF) levels of dopamine (DA), norepinephrine (NE), serotonin (5-HT) and their m...The aim of this study was to investigate the effect of 30 min forebrain ischemia, followed by 120 min reperfusion on extracellular fluid (ECF) levels of dopamine (DA), norepinephrine (NE), serotonin (5-HT) and their metabolites, homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) in the striatum of gerbils, so as to obtain further information on the mechanism of Radix Salviae Miltiorrhizae (RSM)-induced neuroprotection. Microdialysis was used to sample the extracellular space. Dialysate was measured by high performance liquid chromatography with electrochemical detector (HPLC-ED). ECF DA, NE levels increased from basal levels by 282, 227 and 221 folds, by 9.14, 8.51 and 8.25 folds, respectively for the three ischemic duration (0-10; 11-20; 21-30 min). ECF DA, NE, 5-HT levels in the RSM-treated group were significantly decreased as compared with those in the control group during ischemia (P展开更多
Ant colonies self-organize to solve complex problems despite the simplicity of an individual ant＇s brain. Pavement ant Tetramorium caespitum colonies must solve the problem of defending the ter- ritory that they patr...Ant colonies self-organize to solve complex problems despite the simplicity of an individual ant＇s brain. Pavement ant Tetramorium caespitum colonies must solve the problem of defending the ter- ritory that they patrol in search of energetically rich forage. When members of 2 colonies randomly interact at the territory boundary a decision to fight occurs when： 1） there is a mismatch in nest- mate recognition cues and 2） each ant has a recent history of high interaction rates with nestmate ants. Instead of fighting, some ants will decide to recruit more workers from the nest to the fighting location, and in this way a positive feedback mediates the development of colony wide wars. In ants, the monoamines serotonin （5-HT） and octopamine （OA） modulate many behaviors associated with colony organization and in particular behaviors associated with nestmate recognition and ag- gression. In this article, we develop and explore an agent-based model that conceptualizes how in- dividual changes in brain concentrations of 5-HT and OA, paired with a simple threshold-based de- cision rule, can lead to the development of colony wide warfare. Model simulations do lead to the development of warfare with 91% of ants fighting at the end of 1 h. When conducting a sensitivity analysis, we determined that uncertainty in monoamine concentration signal decay influences the behavior of the model more than uncertainty in the decision-making rule or density. We conclude that pavement ant behavior is consistent with the detection of interaction rate through a single timed interval rather than integration of multiple interactions.展开更多
Accurate assessment of the probability of success in an aggressive confrontation with a conspecific is critical to the survival and fitness of the individuals. Various game theory models have examined these assessment...Accurate assessment of the probability of success in an aggressive confrontation with a conspecific is critical to the survival and fitness of the individuals. Various game theory models have examined these assessment strategies under the assumption that contests should favor the animal with the greater resource-holding potential （RHP）, body size typically being the proxy. Mutual assessment asserts that an individual can assess their own RHP relative to their opponent, allowing the inferior animal the chance to flee before incurring unnecessary costs. The model of self-determined persistence, however, assumes that an individual will fight to a set personal threshold, independ- ent of their opponent＇s RHP. Both models have been repeatedly tested using size as a proxy for RHP, with neither receiving unambiguous support. Here we present both morphological and neuro- physiological data from size-matched and mismatched stalk-eyed fly fights. We discovered differ- ing fighting strategies between winners and losers. Winners readily escalated encounters to higher intensity and physical contact and engaged in less low-intensity, posturing behaviors compared with losers. Although these fighting strategies were largely independent of size, they were associ- ated with elevated levels of 5-HT. Understanding the neurophysiological factors responsible for mediating the motivational state of opponents could help resolve the inconsistencies seen in cur- rent game theory models. Therefore, we contend that current studies using only size as a proxy for RHP may be inadequate in determining the intricacies of fighting ability and that future studies investigating assessment strategies and contest outcome should include neurophysiological data.展开更多
Brain aminergic tone was examined in rats with different genetically determined generalized epilepsies and in normal rats. Our previously published database was analyzed to examine if there were functional correlation...Brain aminergic tone was examined in rats with different genetically determined generalized epilepsies and in normal rats. Our previously published database was analyzed to examine if there were functional correlations between brain biogenic amines and their metabolic rates within particular cerebral regions. Rats with genetically determined absence (AbS) and/or audiogenic seizures (AGS) served as models for human generalized non-convulsive and convulsive epilepsies. Tissue concentrations of 5-HT, dopamine (DA) and their main metabolites, as well as tryptophan (TRT), histamine (HA) and noradrenaline (NA) were assayed in different brain regions and analyzed for within-regions correlations in non-stressed conditions. It was found that AbS rats had higher indices of DA-ergic metabolism than non-epileptic controls, but the severity of AbS correlated with a widespread dopaminergic deficiency, as expressed in lowered indices of DA metabolism. AGS exerted no major effects on tissue neurochemistry. Brain DA-ergic and 5HT-ergic metabolic indices (measured as the ratio of the metabolite to the parent transmitter) were closely linked in striatum and pons-medulla of AbS rats. Remarkably, the tissue content of HA in pons-medulla of AbS rats displayed correlations with metabolic ratios of 5HT and DA, which was not seen in normal rats. It is hypothesized that enhanced metabolism of DA and 5HT are at least partial compensatory antiepileptic mechanisms in the brain, and a disturbance of this compensation leads to an aggravation of absence seizures.展开更多
AIM: To evaluate changes in neurotransmission induced by a psychoactive beverage ayahuasca in the hippocampus and amygdala of naive rats. METHODS: The level of monoamines, their main metabolites and amino acid neurotr...AIM: To evaluate changes in neurotransmission induced by a psychoactive beverage ayahuasca in the hippocampus and amygdala of naive rats. METHODS: The level of monoamines, their main metabolites and amino acid neurotransmitters concentrations were quantified using high performance liquid chromatography(HPLC). Four groups of rats were employed: saline-treated and rats receiving 250, 500 and 800 mg/kg of ayahuasca infusion(gavage). Animals were killed 40 min after drug ingestion and the structures stored at-80 ℃ until HPLC assay. The data from all groups were compared using Analysis of variance and Scheffé as post test and P < 0.05 was accepted as significant. RESULTS: The results showed decreased concentrations of glycine(GLY)(0.13 ± 0.03 vs 0.29 ± 0.07, P < 0.001) and γ-aminobutyric acid(GABA)(1.07 ± 0.14 vs 1.73 ± 0.25, P < 0.001) in the amygdala of rats that received 500 of ayahuasca. Animals that ingested 800 mg/kg of ayahuasca also showed a reduction of GLY level(0.11 ± 0.01 vs 0.29 ± 0.07, P < 0.001) and GABA(0.98 ± 0.06 vs 1.73 ± 0.25, P < 0.001). In the hippocampus, increased GABA levels were found in rats that received all ayahuasca doses: 250 mg/kg(1.29 ± 0.19 vs 0.84 ± 0.21, P < 0.05); 500 mg/kg(2.23 ± 038 vs 084 ± 0.21, P < 0.05) and 800 mg/kg(1.98 ± 0.92 vs 0.84 ± 0.21, P < 0.05). In addition, an increased utilization rate of all monoamines was found in the amygdala after ayahuasca administration in doses: 250 mg/kg(noradrenaline: 0.16 ± 0.02 vs 0.36 ± 0.06, P < 0.01; dopamine: 0.39 ± 0.012 vs 2.39 ± 0.84, P < 0.001; serotonin: 1.02 ± 0.22 vs 4.04 ± 0.91, P < 0.001), 500 mg/kg(noradrenaline: 0.08 ± 0.02 vs 0.36 ± 0.06, P < 0.001; dopamine: 0.33 ± 0.19 vs 2.39 ± 0.84, P < 0.001; serotonin: 0.59 ± 0.08 vs 4.04 ± 0.91, P < 0.001) and 800 mg/kg(noradrenaline: 0.16 ± 0.04 vs 0.36 ± 0.06, P < 0.001; dopamine: 0.84 ± 0.65 vs2.39 ± 0.84, P < 0.05; serotonin: 0.36 ± 0.02 vs 4.04 ± 0.91, P < 0.001). CONCLUSION: Our data suggest increased release of inhibitory amino acids by the hippocampus and an increased utilization rate of monoamines by the amygdala after different doses of ayahuasca ingestion.展开更多
文摘Exercise performance depends on both physiological abilities (e.g., muscle strength) and behavioral characteristics (e.g., motivati on). We tested the hypothesis that evoluti on of in creased aerobic exercise performanee can be facilitated by evolution of neuropsychological mechanisms responsible for motivation to undertake physical activity. We used a unique model system: lines of bank voles Myodes glareolus selected for high swim-induced aerobic metabolism ("aerobic" A lines). In gen eration 21, voles from the 4 A lines achieved a 57% higher /y voluntary maximum" swiminduced aerobic metabolism (V02swim) than voles from 4 unselected,"control" C lines. In C lines, V02swim was 9% lower than the maximum forced-exercise aerobic metabolism (VO2run;P= 0.007), while in A lines it was even higher than VO2run, although not significantly (4%, P=0.15). Thus, we hypothesized that selection changed both the aerobic capacity and the neuronal mechanisms behi nd motivation to un dertake activity. We investigated the influe nee of reuptake in hibitors of dopamine (DARI), serotonin (SSRI), and norepinephrine (NERI) on VOaSwim. The drugs decreased V02swim both in C and A lines (% decrease compared with saline: DARI 8%, P< 0.001;SSRI 6%, P< 0.001;NERI 8%, P< 0.001), but the proportional response differed between selection directions only for NERI (stronger effect in C lines: P= 0.008) and the difference was marginally non-significant for SSRI (P= 0.07) and DARI (P= 0.06). Thus, the results suggest that all the 3 monoamines are involved in signaling pathways controlling the motivation to be active and that norepinephrine could have played a role in the evolution of increased aerobic exercise performance in our animal model.
文摘The aim of this study was to determine the time course of changes in extracellular fluid (ECF) concentrations of purines, amino acids, monoamines, and their metabolites in the striatum of rats during ischemia and reperfusion, using intracerebral microdialysis as the sampling technique. In rats subjected to 20 min forebrain ischemia by four-vessel occlusion, the concentrations of adenosine (Ade), inosine (Ino) and hypoxanthine (Hyp) were found to rise markedly. These changes were accompanied by dramatically elevated levels of aspartate (Asp), glutamate (Glu), taurine (Tau), γ-aminobutyric acid (GABA), dopamine (DA) and norepinephrine (NE), all of which gradually returned to baseline following reperfusion. Concomitantly, the levels of metabolite 3, 4-dihydroxyphenylacetic acid (DOPAC) . homovanillic acid (HVA), 5-hydroxyindole-3-acetic acid (5-HIAA) and xanthine (Xan) decreased during ischemia and gradually recovered 60～ 90 min after reperfusion. It was concluded that during global brain ischemia, the ECF is flooded with both potentially harmful (e. g. Asp, Glu, DA) and protective (e. g. Tau, GABA, Ade) agents.
基金supported by the Crafoord Foundationthe Lundbeck Foundationthe Danish Medical Research Council
文摘Monoamine neurotransmitters play an important role in the modulation of sensory, motor and autonomic functions in the spinal cord. Although traditionally it is believed that in mammalian spinal cord, monoamine neurotransmitters mainly originate from the brain, accumulating evidence indicates that especially when the spinal cord is injured, they can also be produced in the spinal cord. In this review, I will present evidence for a possible pathway for two-step synthesis of dopamine and serotonin in the spinal cord. Published data from different sources and unpublished data from my own ongoing projects indicate that monoenzymatic cells expressing aromatic L-amino acid decarboxylase（AADC）, tyrosine hydroxylase（TH） or tryptophan hydroxylase（TPH） are present in the spinal cord and that these TH and THP cells often lie in close proximity to AADC cells. Prompted by the above evidence, I hypothesize that dopamine and serotonin could be synthesized sequentially in two monoenzymatic cells in the spinal cord via a TH-AADC and a TPH-AADC cascade respectively. The monoamines synthesized through this pathway may compensate for lost neurotransmitters following spinal cord injury and also may play specific roles in the recovery of sensory, motor and autonomic functions.
基金supported by the Research Project of the Shanghai Health Commission,No.2020YJZX0111(to CZ)the National Natural Science Foundation of China,Nos.82021002(to CZ),82272039(to CZ),82171252(to FL)+1 种基金a grant from the National Health Commission of People’s Republic of China(PRC),No.Pro20211231084249000238(to JW)Medical Innovation Research Project of Shanghai Science and Technology Commission,No.21Y11903300(to JG).
文摘Nowadays,presynaptic dopaminergic positron emission tomography,which assesses deficiencies in dopamine synthesis,storage,and transport,is widely utilized for early diagnosis and differential diagnosis of parkinsonism.This review provides a comprehensive summary of the latest developments in the application of presynaptic dopaminergic positron emission tomography imaging in disorders that manifest parkinsonism.We conducted a thorough literature search using reputable databases such as PubMed and Web of Science.Selection criteria involved identifying peer-reviewed articles published within the last 5 years,with emphasis on their relevance to clinical applications.The findings from these studies highlight that presynaptic dopaminergic positron emission tomography has demonstrated potential not only in diagnosing and differentiating various Parkinsonian conditions but also in assessing disease severity and predicting prognosis.Moreover,when employed in conjunction with other imaging modalities and advanced analytical methods,presynaptic dopaminergic positron emission tomography has been validated as a reliable in vivo biomarker.This validation extends to screening and exploring potential neuropathological mechanisms associated with dopaminergic depletion.In summary,the insights gained from interpreting these studies are crucial for enhancing the effectiveness of preclinical investigations and clinical trials,ultimately advancing toward the goals of neuroregeneration in parkinsonian disorders.
基金supported by the Ministry of Science and Technology of China (2014CB239402, 2013CB834505, 2013CB834804)the National Natural Science Foundation of China (91427303, 21372232, 21204052)+1 种基金the Key Research Programme of the Chinese Academy of Sciences (KGZD-EW-T05)the Foundation of Director of TIPC
文摘We develop here a simple wet chemistry to prepare covalent functionalized graphenes （FGs） through epoxide aminolysis espe- cially under alkaline aqueous condition. Remarkably, a series of typical monoamines, such as industrial Huntsman Jeffamine M-2070 and M-2005 polymer with hydrophilic or hydrophobic polyetheramine chains, positively-charged 2-amino-N,N,N- trimethylpropanaminium, negatively-charged sulfanilic acid, even oligopeptide sequence, can be effectively grafted on the platelets of graphene oxide precursor with covalent functionalization and partially reduced features. This strategy provides the researchers a facile and convenient approach to design and synthesize solution processable, biocompatible and functionalized graphenes for the potent applications in electronic inks, drug carriers and biomedicines. Expansion of the current study is actively ongoing in our laboratory.
文摘Objective: To study the mechanism of acupuncture in treating simple obesity. Methods: Central nerve push-pull perfusion and biochemical technique were used to observe the effect of acupuncture on the obese parameters, changes of monoamine transmitters and activity of ATPase in the lateral hypothalamic area (LHA) of obese rats. Results: Noradrenaline (NA) level in LHA of obese rats was higher but serotonin (5-HT) level and ATPase activity were lower than those in normal rats. After acupuncture treatment, in the same time of reducing body weight, NA level in LHA of rats was reduced, and 5-HT level and ATPase activity in it were increased.(P<0.05 and P<0.01). Conclusion:The effective regulation on LHA of obese rats is possibly one of the key factors in anti-obesity effect of acupuncture.
基金Project supported by the World Health Organization.
文摘In recent years, the importance of hypothalamic defence area (HDA) has attracted more and more attention. Many researchers demonstrated that HDA plays a very important role in cardiovascular and behavioral regulations. However, so far release of central neurotransmitters during excitement of HDA is unknown. The present study showed that stimulation of HDA could increase the contents of monoamines and their metabolites, especially the latter, in the cerebrospinal fluid (CSF) of rabbits.
文摘Type-B monoamine oxidase inhibitors,encompassing selegiline,rasagiline,and safinamide,are available to treat Parkinson's disease.These drugs ameliorate motor symptoms and improve motor fluctuation in the advanced stages of the disease.There is also evidence suppo rting the benefit of type-B monoamine oxidase inhibitors on non-motor symptoms of Parkinson's disease,such as mood deflection,cognitive impairment,sleep disturbances,and fatigue.Preclinical studies indicate that type-B monoamine oxidase inhibitors hold a strong neuroprotective potential in Parkinson's disease and other neurodegenerative diseases for reducing oxidative stress and stimulating the production and release of neurotrophic factors,particularly glial cell line-derived neurotrophic factor,which suppo rt dopaminergic neurons.Besides,safinamide may interfere with neurodegenerative mechanisms,countera cting excessive glutamate overdrive in basal ganglia motor circuit and reducing death from excitotoxicity.Due to the dual mechanism of action,the new generation of type-B monoamine oxidase inhibitors,including safinamide,is gaining interest in other neurological pathologies,and many supporting preclinical studies are now available.The potential fields of application concern epilepsy,Duchenne muscular dystrophy,multiple scle rosis,and above all,ischemic brain injury.The purpose of this review is to investigate the preclinical and clinical pharmacology of selegiline,rasagiline,and safinamide in Parkinson's disease and beyond,focusing on possible future therapeutic applications.
基金This work was supported by the Science and Technology Project of Haihe Laboratory of Modern Chinese Medicine,China(Grant No.:22HHZYSS00003)the Science and Technology Program of Tianjin,China(Grant No.:22ZYJDSS00100)The authors would like to thank the support from Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine,China(Grant No:ZYYCXTD-D-202002).
文摘Alzheimer's disease(AD)is gradually increasing in prevalence and the complexity of its pathogenesis has led to a lengthy process of developing therapeutic drugs with limited success.Faced with this challenge,we proposed using a state-of-the-art drug screening algorithm to identify potential therapeutic compounds for AD from traditional Chinese medicine formulas with strong empirical support.We developed four deep neural network(DNN)models for AD drugs screening at the disease and target levels.The AD model was trained with compounds labeled for AD activity to predict active compounds at the disease level,while the acetylcholinesterase(AChE),monoamine oxidase-A(MAO-A),and 5-hydroxytryptamine 6(5-HT6)models were trained for specific AD targets.All four models performed excellently and were used to identify potential AD agents in the Kaixinsan(KXS)formula.High-scoring compounds underwent experimental validation at the enzyme,cellular,and animal levels.Compounds like 2,4-di-tert-butylphenol and elemicin showed significant binding and inhibitory effects on AChE and MAO-A.Additionally,13 compounds,includingα-asarone,penetrated the blood-brain barrier(BBB),indicating potential brain target binding,and eight compounds enhanced microglialβ-amyloid phagocytosis,aiding in clearing AD pathological substances.Our results demonstrate the effectiveness of deep learning models in developing AD therapies and provide a strong platform for AD drug discovery.
文摘Objective: In the manuscript titled Monoamine Oxidase-B Inhibitor Rasagiline Effects on Motor and Non-Motor Symptoms in Individuals with Parkinsons Disease: A Systematic Review and Meta-Analysis, the objective was to conduct a systematic review with meta-analysis to investigate the effects that Rasagiline has on motor and non-motor symptoms in individuals with PD. Introduction: Rasagiline is a second-generation monoamine oxidase-B (MAO-B) inhibitor used both as monotherapy and adjunctive therapy for Parkinsons Disease (PD). Methods: A systematic literature search and meta-analysis were performed with randomized control trials that investigated the effects of Rasagiline on motor and non-motor symptoms in individuals with PD. The systematic search was conducted in PubMed, Cochrane, and EBSCO databases. Methodological quality was assessed using the Cochrane Grading Recommendations Assessment, Development and Evaluation approach. Results: Fourteen studies were included in our review. There were trivial to small and statistically significant improvements in motor symptoms for individuals with PD treated with Rasagiline compared to placebo. Non-motor symptoms showed no significant improvement with Rasagiline compared to placebo in five of six meta-analyses. Results were based on very low to moderate certainty of evidence. Conclusion: 1 mg/day Rasagiline significantly improved Parkinsonian motor symptoms in individuals with PD compared with placebo. For all outcomes, the 1 mg/day Rasagiline group was favored over the placebo group.
基金Natural Science Foundation of Jiangsu Province,Grant/Award Number:BK20210062National Natural Science Foundation of China,Grant/Award Number:82172054Project of Key Laboratory of Organic Synthesis of Jiangsu Province,College of Chemistry,Chemical Engineering and Materials Science,Soochow University,Grant/Award Number:KJS2326。
文摘Monoamine oxidases(MAOs)are a class of flavin enzymes that are mainly present in the outer membrane of mitochondria and play a crucial role in maintaining the homeostasis of monoamine neurotransmitters in the central nervous system.Furthermore,expression of MAOs is associated with the functions of peripheral organs.Dysfunction of MAOs is relevant in a variety of diseases such as neurodegenerative diseases,heart failure,metabolic disor-ders,and cancers.Monoamine oxidases have two isoenzymes,namely,monoamine oxidase A(MAO-A)and monoamine oxidase B(MAO-B).Therefore,the development of reliable and specific methods to detect these two isoenzymes is of great significance for the in-depth understanding of their functions in biological systems,and for further promoting the clinical diag-nosis and treatment of MAO-related diseases.This review mainly focuses on the advances in small molecular probes for the specific imaging of MAO-A and MAO-B,including radiolabeled probes,fluorescent probes,and a 19F magnetic resonance imaging probe.In addition,applications of these probes for detecting MAO expression levels in cells,tissues,animal models,and patients are described.Finally,the challenges and perspectives of developing novel MAO imaging probes are also highlighted.
基金National Natural Science Foundation(Grant No.813 73372)the Open Foundation of State Key Laboratory of Natural and Biomimetic Drugs(Grant No.SKL2012004)Specialized Research Fund for the Doctoral Program of Higher Education of China(Grant No.20110001110021 and 20130001110059)
文摘Abstract： In the presem study, we simultaneously quantified the levels of monoamine neurotransmitters （MANTs） and their metabolites （levodopa, norepinephrine, epinephrine, dopamine, 5-HT, 3,4-dihydroxyphenylacetic acid, homovanillic acid and 5-hydroxyindole-3-acetic acid） in different brain subregions of rats using a newly developed simple, sensitive and selective high-performance liquid chromatography with fluorescence detection （HPLC-FLD） method. In this new HPLC-FLD method, analytes were directly extracted and separated without deriveatization step within 20 min. The FLD wavelength was set at 280 nm and 330 nm for excitation and emission, respectively. The analytes were separated on an Agilent Eclipse Plus Cls column （4.6 mm×150 mm, 5.0 μm） equipped with an Agilent XDB-C18 security guard column （4.6 mm×12.5 mm, 5.0 lam）, and the column temperature was maintained at 35 ℃. The mobile phase for elution was isocratic. The mobile phase consisted of citric acid buffer （50 mmol/L citric acid, 50 mmol/L sodium acetate, 0.5 mmol/L octane sulfonic acid sodium salt, 0.5 mmol/L Na2EDTA and 5 mmol/L triethylamine, pH 3.8） and methanol （90：10, v/v） at a flow rate of 1.0 mL/min. The detection limit （DL） was 0.9-23 nM for all the MANTs and their metabolites with a sample volume of 50 μL. The method was shown to be highly reproducible in terms of peak area （intraday, 0.08%-1.85% RSD, n = 5）. The simultaneous measurement of these MANTs and their metabolites improved our understanding of the neurochemistry in the central nervous system （CNS） in relation to different addictive drugs （methamphetamine, heroin and their mixture） in drug-addicted rat models.
文摘Aggression is a common behavioral trait shared in many animals, including both vertebrates and invertebrates. However, the type and intensity of agonistic encounters and displays can vary widely both across and within species, resulting in complicated or subjective interpretations that create difficulties in developing theoretical models that can be widely applied. The need to easily and objectively identify quantifiable behaviors and their associated morphologies becomes especially important when attempting to decipher the neurological mechanisms underlying this complex behavior. Monoamines, neuropeptides, and pheromones have been implicated as important neuromodulators for agonistic displays in both invertebrates and vertebrates. Ad- ditionally, recent breakthroughs in insect research have revealed exciting proximate mechanisms important in aggression that may be broadly relevant, due to the relatively high conservation of these neurochemical systems across animal taxa. In this review, we present the latest research demonstrating the importance of monoamines, neuropeptides, and pheromones as neuromodulators for aggression across a variety of insect species. Additionally, we describe the stalk-eyed fly as a model system for studying aggres- sion, which integrates physiological, morphological, and neurochemical approaches in exploring detailed mechanisms responsible for this common yet complex behavior. We conclude with our perspective on the most promising lines of future research aimed at understanding the proximate and ultimate mechanisms underlying aggressive behaviors .
文摘The organization of the brain serotonergic system appears to have been highly conserved across the vertebrate subphylum. In fish as well as in other vertebrates, brain serotonin （5-HT）, mainly acts as a neuromodulator with complex effects on multiple functions. It is becoming increasingly clear that acute and chronic increase in brain 5-HT neurotransmission have very different effects. An acute 5-HT activation, which is seen in both winners and losers of agonistic interactions, could be related to a general arousal effect, whereas the chronic activation observed in subordinate fish is clearly linked to the behavioral inhibition displayed by these individuals. Fish displaying diver- gent stress coping styles （proactive vs. reactive） differ in 5-HT functions. In teleost fish, brain monoaminergic function is also related to life history traits.
文摘Effects of acupuncture on the levels of neurotransmitters in the raphe nuclei were investigated in obeserats.It was found that the levels of tryptophan (Trp) and 5-hydroxyindoleacetic acid (5-HIAA) wereincreased,and 5-hydroxytryptamine (5-HT) level and 5-HT/5-HIAA ratio decreased in the raphe nucleiof the obese group as compared with the normal group;and that acupuncture could produce weightreduction,increase the 5-HT level and 5-HT/5-HIAA ratio,and decrease the contents of Trp and5-HIAA,but did not change the levels of dopamine (DA) and noradrenaline (NA).It is indicated thatbenign regulative action of acupuncture on 5-HT and its metabolism in the raphe nuclei is possibly oneof the factors for reducing weight by acupuncture.
文摘The aim of this study was to investigate the effect of 30 min forebrain ischemia, followed by 120 min reperfusion on extracellular fluid (ECF) levels of dopamine (DA), norepinephrine (NE), serotonin (5-HT) and their metabolites, homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) in the striatum of gerbils, so as to obtain further information on the mechanism of Radix Salviae Miltiorrhizae (RSM)-induced neuroprotection. Microdialysis was used to sample the extracellular space. Dialysate was measured by high performance liquid chromatography with electrochemical detector (HPLC-ED). ECF DA, NE levels increased from basal levels by 282, 227 and 221 folds, by 9.14, 8.51 and 8.25 folds, respectively for the three ischemic duration (0-10; 11-20; 21-30 min). ECF DA, NE, 5-HT levels in the RSM-treated group were significantly decreased as compared with those in the control group during ischemia (P
文摘Ant colonies self-organize to solve complex problems despite the simplicity of an individual ant＇s brain. Pavement ant Tetramorium caespitum colonies must solve the problem of defending the ter- ritory that they patrol in search of energetically rich forage. When members of 2 colonies randomly interact at the territory boundary a decision to fight occurs when： 1） there is a mismatch in nest- mate recognition cues and 2） each ant has a recent history of high interaction rates with nestmate ants. Instead of fighting, some ants will decide to recruit more workers from the nest to the fighting location, and in this way a positive feedback mediates the development of colony wide wars. In ants, the monoamines serotonin （5-HT） and octopamine （OA） modulate many behaviors associated with colony organization and in particular behaviors associated with nestmate recognition and ag- gression. In this article, we develop and explore an agent-based model that conceptualizes how in- dividual changes in brain concentrations of 5-HT and OA, paired with a simple threshold-based de- cision rule, can lead to the development of colony wide warfare. Model simulations do lead to the development of warfare with 91% of ants fighting at the end of 1 h. When conducting a sensitivity analysis, we determined that uncertainty in monoamine concentration signal decay influences the behavior of the model more than uncertainty in the decision-making rule or density. We conclude that pavement ant behavior is consistent with the detection of interaction rate through a single timed interval rather than integration of multiple interactions.
文摘Accurate assessment of the probability of success in an aggressive confrontation with a conspecific is critical to the survival and fitness of the individuals. Various game theory models have examined these assessment strategies under the assumption that contests should favor the animal with the greater resource-holding potential （RHP）, body size typically being the proxy. Mutual assessment asserts that an individual can assess their own RHP relative to their opponent, allowing the inferior animal the chance to flee before incurring unnecessary costs. The model of self-determined persistence, however, assumes that an individual will fight to a set personal threshold, independ- ent of their opponent＇s RHP. Both models have been repeatedly tested using size as a proxy for RHP, with neither receiving unambiguous support. Here we present both morphological and neuro- physiological data from size-matched and mismatched stalk-eyed fly fights. We discovered differ- ing fighting strategies between winners and losers. Winners readily escalated encounters to higher intensity and physical contact and engaged in less low-intensity, posturing behaviors compared with losers. Although these fighting strategies were largely independent of size, they were associ- ated with elevated levels of 5-HT. Understanding the neurophysiological factors responsible for mediating the motivational state of opponents could help resolve the inconsistencies seen in cur- rent game theory models. Therefore, we contend that current studies using only size as a proxy for RHP may be inadequate in determining the intricacies of fighting ability and that future studies investigating assessment strategies and contest outcome should include neurophysiological data.
文摘Brain aminergic tone was examined in rats with different genetically determined generalized epilepsies and in normal rats. Our previously published database was analyzed to examine if there were functional correlations between brain biogenic amines and their metabolic rates within particular cerebral regions. Rats with genetically determined absence (AbS) and/or audiogenic seizures (AGS) served as models for human generalized non-convulsive and convulsive epilepsies. Tissue concentrations of 5-HT, dopamine (DA) and their main metabolites, as well as tryptophan (TRT), histamine (HA) and noradrenaline (NA) were assayed in different brain regions and analyzed for within-regions correlations in non-stressed conditions. It was found that AbS rats had higher indices of DA-ergic metabolism than non-epileptic controls, but the severity of AbS correlated with a widespread dopaminergic deficiency, as expressed in lowered indices of DA metabolism. AGS exerted no major effects on tissue neurochemistry. Brain DA-ergic and 5HT-ergic metabolic indices (measured as the ratio of the metabolite to the parent transmitter) were closely linked in striatum and pons-medulla of AbS rats. Remarkably, the tissue content of HA in pons-medulla of AbS rats displayed correlations with metabolic ratios of 5HT and DA, which was not seen in normal rats. It is hypothesized that enhanced metabolism of DA and 5HT are at least partial compensatory antiepileptic mechanisms in the brain, and a disturbance of this compensation leads to an aggravation of absence seizures.
基金Supported by Funda o de Amparo a Pesquisa do Estado de S o PauloCoordena o de Aperfei oamento de Pessoal de Nível Superior+1 种基金Conselho Nacional de Desenvolvimento Científico e TecnológicoInstituto Nacional de Neurociência Translacional
文摘AIM: To evaluate changes in neurotransmission induced by a psychoactive beverage ayahuasca in the hippocampus and amygdala of naive rats. METHODS: The level of monoamines, their main metabolites and amino acid neurotransmitters concentrations were quantified using high performance liquid chromatography(HPLC). Four groups of rats were employed: saline-treated and rats receiving 250, 500 and 800 mg/kg of ayahuasca infusion(gavage). Animals were killed 40 min after drug ingestion and the structures stored at-80 ℃ until HPLC assay. The data from all groups were compared using Analysis of variance and Scheffé as post test and P < 0.05 was accepted as significant. RESULTS: The results showed decreased concentrations of glycine(GLY)(0.13 ± 0.03 vs 0.29 ± 0.07, P < 0.001) and γ-aminobutyric acid(GABA)(1.07 ± 0.14 vs 1.73 ± 0.25, P < 0.001) in the amygdala of rats that received 500 of ayahuasca. Animals that ingested 800 mg/kg of ayahuasca also showed a reduction of GLY level(0.11 ± 0.01 vs 0.29 ± 0.07, P < 0.001) and GABA(0.98 ± 0.06 vs 1.73 ± 0.25, P < 0.001). In the hippocampus, increased GABA levels were found in rats that received all ayahuasca doses: 250 mg/kg(1.29 ± 0.19 vs 0.84 ± 0.21, P < 0.05); 500 mg/kg(2.23 ± 038 vs 084 ± 0.21, P < 0.05) and 800 mg/kg(1.98 ± 0.92 vs 0.84 ± 0.21, P < 0.05). In addition, an increased utilization rate of all monoamines was found in the amygdala after ayahuasca administration in doses: 250 mg/kg(noradrenaline: 0.16 ± 0.02 vs 0.36 ± 0.06, P < 0.01; dopamine: 0.39 ± 0.012 vs 2.39 ± 0.84, P < 0.001; serotonin: 1.02 ± 0.22 vs 4.04 ± 0.91, P < 0.001), 500 mg/kg(noradrenaline: 0.08 ± 0.02 vs 0.36 ± 0.06, P < 0.001; dopamine: 0.33 ± 0.19 vs 2.39 ± 0.84, P < 0.001; serotonin: 0.59 ± 0.08 vs 4.04 ± 0.91, P < 0.001) and 800 mg/kg(noradrenaline: 0.16 ± 0.04 vs 0.36 ± 0.06, P < 0.001; dopamine: 0.84 ± 0.65 vs2.39 ± 0.84, P < 0.05; serotonin: 0.36 ± 0.02 vs 4.04 ± 0.91, P < 0.001). CONCLUSION: Our data suggest increased release of inhibitory amino acids by the hippocampus and an increased utilization rate of monoamines by the amygdala after different doses of ayahuasca ingestion.
