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Surprising Separation of Cannabinoid Physical Dependence and Withdrawal in an Invertebrate Model

Surprising Separation of Cannabinoid Physical Dependence and Withdrawal in an Invertebrate Model
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摘要 Planarians have mammalian-like neurotransmitter systems and have been established as a novel in vivo model for neuropharmacology. In previous research, planarians that have been exposed to the cannabinoid receptor (CB-R) agonist WIN 55,212-2 for 1 h displayed abstinence-induced withdrawal when tested in drug-free, but not in drug-containing, water. The goals of the present study were to extend previous work and to further establish a cannabinoid behavioral model with planarians. The results showed 1) four different CB-R antagonists (AM251, AM281, SLV319 and SR144528) dose-relatedly blocked development of physical dependence induced by two different CB-R agonists (WIN 55,212-2 and JWH251);2) none of the same four antagonists (AM251, AM281, SLV319 or SR144528) precipitated withdrawal;3) short wavelength (254 nm), but not long wavelength (366 nm), ultraviolet (UV) light attenuated abstinence-induced withdrawal from WIN 55,212-2, while short wavelength UV light induced moderate withdrawal behavior. The results confirm the use of a planarian model as a simple yet robust way to study development of physical dependence to cannabinoid agonists. The effect of UV irradiation adds to the evidence that the results are receptor-related. The results also give rise to the surprising suggestion, within the limitations of the methodology, that development of cannabinoid physical dependence and antagonist-induced precipitated withdrawal might be separable phenomena in planarians. Planarians have mammalian-like neurotransmitter systems and have been established as a novel in vivo model for neuropharmacology. In previous research, planarians that have been exposed to the cannabinoid receptor (CB-R) agonist WIN 55,212-2 for 1 h displayed abstinence-induced withdrawal when tested in drug-free, but not in drug-containing, water. The goals of the present study were to extend previous work and to further establish a cannabinoid behavioral model with planarians. The results showed 1) four different CB-R antagonists (AM251, AM281, SLV319 and SR144528) dose-relatedly blocked development of physical dependence induced by two different CB-R agonists (WIN 55,212-2 and JWH251);2) none of the same four antagonists (AM251, AM281, SLV319 or SR144528) precipitated withdrawal;3) short wavelength (254 nm), but not long wavelength (366 nm), ultraviolet (UV) light attenuated abstinence-induced withdrawal from WIN 55,212-2, while short wavelength UV light induced moderate withdrawal behavior. The results confirm the use of a planarian model as a simple yet robust way to study development of physical dependence to cannabinoid agonists. The effect of UV irradiation adds to the evidence that the results are receptor-related. The results also give rise to the surprising suggestion, within the limitations of the methodology, that development of cannabinoid physical dependence and antagonist-induced precipitated withdrawal might be separable phenomena in planarians.
出处 《Pharmacology & Pharmacy》 2018年第12期489-502,共14页 药理与制药(英文)
关键词 CANNABINOID Physical DEPENDENCE WITHDRAWAL PLANARIANS UV Light Cannabinoid Physical Dependence Withdrawal Planarians UV Light
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