Moreau J L, Jenck F, Martin J R, Perrin S, Haefely W E
Pharma Division, F. Hoffmann-La Roche, Basel, Switzerland.
Psychopharmacology (Berl). 1993;110(1-2):140-4. doi: 10.1007/BF02246963.
This study investigated the possible involvement of 5HT1C receptors in the development of depressive states and in the mode of action of antidepressants. The effects of repeated unpredictable mild stress (a regimen known to induce an anhedonic state in the rat) and of chronic administration of either of two recognized antidepressant treatments (sleep deprivation or inhibition of monoamine oxidase type A) in rats were studied on a 5HT1C receptor initiated response, i.e. mCPP-induced penile erection. A 3-week period of repeated, but unpredictable exposure to mild stressors induced a shift to the left of the dose-response curve for mCPP-induced penile erection. In contrast, 72-h REM sleep deprivation resulted in a shift to the right of the mCPP dose-response curve and 10-day administration of the monoamine oxidase type A inhibitor moclobemide (20 mg/kg IP bid) also resulted in a decreased number of mCPP-induced penile erections. These findings support the hypothesis that neuronal activities initiated via 5HT1C receptor stimulation may play a role in the pathophysiology and treatment of depression.
本研究调查了5HT1C受体在抑郁状态发展及抗抑郁药作用模式中可能的参与情况。研究了重复不可预测轻度应激（一种已知可在大鼠中诱导快感缺失状态的方案）以及两种公认的抗抑郁治疗（睡眠剥夺或A型单胺氧化酶抑制）之一在大鼠中对5HT1C受体引发反应（即mCPP诱导的阴茎勃起）的影响。为期3周的重复但不可预测的轻度应激源暴露导致mCPP诱导阴茎勃起的剂量反应曲线向左移动。相反，72小时快速眼动睡眠剥夺导致mCPP剂量反应曲线向右移动，并且连续10天给予A型单胺氧化酶抑制剂吗氯贝胺（20mg/kg腹腔注射，每日两次）也导致mCPP诱导阴茎勃起的数量减少。这些发现支持了这样的假说，即通过5HT1C受体刺激引发的神经元活动可能在抑郁症的病理生理学和治疗中起作用。
