ANTIDEPRESSANT-LIKE EFFECTS OF DOPAMINE AGONISTS IN AN ANIMAL-MODEL OF DEPRESSION
ANTIDEPRESSANT-LIKE EFFECTS OF DOPAMINE AGONISTS IN AN ANIMAL-MODEL OF DEPRESSION
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DOI：
10.1016/0006-3223(92)90119-k
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发表时间：
1992-05-01
影响因子：
10.6
通讯作者：
WILLNER, P
中科院分区：
文献类型：
--
作者：
MUSCAT, R;PAPP, M;WILLNER, P
慢性暴露于轻度不可预测的压力（CMS）之前已被发现会导致抗抑郁剂可逆的减少可口的甜溶液的消费。有证据表明，抗抑郁药在该模型中的作用是通过增加多巴胺（DA）突触的传递来介导的。本研究调查了另一种已知可增加DA系统功能反应性的治疗方法，即间歇性给予DA受体激动剂，是否具有抗抑郁样作用。在三项大鼠实验中，CMS诱导的蔗糖消耗减少可通过每周两次注射喹吡罗（100-200 μ g/kg）或溴隐亭（2.5 mg/kg）三至四次而逆转。这种效应持续了几个星期，当它们减弱时，可以通过单次额外注射喹吡罗来恢复。与三环类抗抑郁药一样，喹吡罗的作用被雷氯必利逆转，在蔗糖消耗试验前立即急性给药;非应激对照动物的蔗糖摄入量没有变化。结果表明，间歇性给药的DA受体激动剂值得调查作为一种新的策略，用于治疗抑郁症。
Chronic exposure to mild unpredictable stress (CMS) has previously been found to cause an antidepressant-reversible decrease in the consumption of palatable sweet solutions. There is evidence that the effect of antidepressants in this model is mediated by an increase in transmission at dopamine (DA) synapses. The present study investigated whether another treatment known to increase the functional responsiveness of DA systems, intermittent administration of DA agonists, would have antidepressant-like effects. In three experiments in rats, CMS-induced decreases in sucrose consumption were reversed by three to four twice-weekly injections of quinpirole (100-200-mu-g/kg) or bromocriptine (2.5 mg/kg). The effects lasted for several weeks, and when they waned, could be reinstated by a single additional injection of quinpirole. As with tricyclic antidepressants, the effect of quinpirole was reversed by raclopride, administered acutely immediately prior to a sucrose consumption test; there were no changes in sucrose intake in nonstressed control animals. The results suggest that intermittent administration of DA agonists merits investigation as a novel strategy for the treatment of depression.