摘要
幼年雄性昆明种小鼠(出生后第4天到第21天)连续给予氟西汀(10 mg.kg-1,ip,qd),给药结束后将其正常饲养至成年(出生后约10周)。研究其行为学改变,以及慢性给予胍丁胺抗抑郁效应及其对海马腺苷酸环化酶(AC)活性的影响。研究发现,幼年注射氟西汀的小鼠成年后在开场实验中活动显著减少,而在新奇抑制摄食实验中进食潜伏期明显延长,在小鼠悬尾实验中显著延长小鼠不动时间,表现出"抑郁样"行为改变。胍丁胺连续给药(10 mg.kg-1,ig,bid)3周后显著增加幼年注射氟西汀成年小鼠的开场活动次数,并缩短其摄食潜伏期。单次给予胍丁胺(40 mg.kg-1,ig)在小鼠悬尾实验中能显著缩短模型小鼠的累计不动时间,而在放射免疫实验中显著增强海马AC活性。上述结果表明,幼年小鼠长期给予氟西汀能致小鼠成年后"抑郁样"行为改变,胍丁胺在该模型动物上则表现出抗抑郁活性,并且可能与增强海马AC活性有关。
This study is to explore a behavioral and pathological model for depression in mice, and evaluate the anti-depressant-like effect of agmatine. Neonatal Kunming mice were treated with fluoxetine （10 mg.kg^-1, ip, qd） for 17 d （between day 4 and 21 after birth）, and then the mice were normally housed till being adult （about 10 weeks after birth）. The behaviors of the mice were measured by using open-field test, novelty suppressed feeding test and tail-suspension test. Hippocampal adenylate cyclase （AC） activity was measured by radioimmunoassay. Neonatal exposure to fluoxetine induced a ＂depression-like＂ behaviors in the adult mice, shown as the decreased locomotor activity, increased feeding latency and immobility time in the open-field test, novelty suppressed feeding test, and tail-suspension test, respectively. Chronic agmatine treatment （10 mg.kg^-1, ig, bid） for 3 weeks significantly increased the locomotor activity, and decreased the feeding latency in the neonatal fluoxetine exposed mice. Furthermore, single treatment with agmatine （40 mg.kg^-1, ig） also decreased the immobility time in the tail-suspension test, and increased the hippocampal AC activity in the mice. These results indicate that neonatal exposure to fluoxetine induces depressive-like behaviors in the adult mice. Agmatine reverses these behaviors, which may be closely related to the enhancement of the hippocampal AC activity.
出处
《药学学报》
CAS
CSCD
北大核心
2009年第7期716-721,共6页
Acta Pharmaceutica Sinica
基金
国家自然科学基金资助项目(30300419
30400600
30472018)
全军医药卫生科研基金(06MA304)
国家重点基础研究发展计划(973计划)资助项目(2007CB512307)
国家高技术研究发展计划(863计划)资助项目(2008AA02Z402)
