Brugge K L, Hingtgen J N, Aprison M H
Pharmacol Biochem Behav. 1987 Feb;26(2):287-91. doi: 10.1016/0091-3057(87)90120-1.
Since reserpine precipitates depression in some hypertensive patients, we tested this drug on our animal model of depression. The present experiment was designed to measure the effects of chronic reserpine treatment on 5-hydroxytryptophan (5-HTP) induced behavioral depression in rats trained on a food reinforcement operant schedule. Based on the Aprison et al. model of depression involving the serotonergic system, we predicted the development of receptor supersensitivity of postsynaptic serotonin (5-HT) receptors due to the decreased release of this neurotransmitter as a consequence of chronic reserpine treatment. Rats were trained on a VI 1 reinforcement schedule and then divided into 3 chronic treatment groups. One received daily injections of a placebo, another 0.025 mg/kg reserpine and the third 0.05 mg/kg reserpine. We found that 5-HTP induced behavioral depression was potentiated in rats chronically treated with reserpine, thus suggesting the development of supersensitive 5-HT receptors. These results support the hypothesis that in some types of human depression a decreased release of 5-HT occurs of sufficient duration to permit the subsequent development of supersensitive 5-HT receptors.
由于利血平会使一些高血压患者出现抑郁症状，我们在我们的抑郁症动物模型上对这种药物进行了测试。本实验旨在测量长期使用利血平治疗对按食物强化操作性程序训练的大鼠中5-羟色氨酸（5-HTP）诱导的行为性抑郁的影响。基于阿普里森等人涉及血清素能系统的抑郁症模型，我们预测由于长期使用利血平治疗导致这种神经递质释放减少，突触后5-羟色胺（5-HT）受体将出现超敏反应。大鼠按固定间隔1分钟强化程序进行训练，然后分为3个长期治疗组。一组每天注射安慰剂，另一组注射0.025mg/kg利血平，第三组注射0.05mg/kg利血平。我们发现，在长期接受利血平治疗的大鼠中，5-HTP诱导的行为性抑郁增强，因此提示5-HT受体出现超敏反应。这些结果支持以下假设：在某些类型的人类抑郁症中，5-HT的释放减少持续足够长的时间，从而使得随后5-HT受体出现超敏反应。
