Gambarana C, Ghiglieri O, Tagliamonte A, D'Alessandro N, de Montis M G
Institute of Pharmacology, University of Siena, Italy.
Pharmacol Biochem Behav. 1995 Feb;50(2):147-51. doi: 10.1016/0091-3057(94)00274-m.
Although the neurochemical effects of chronic imipramine (IMI) treatment have been related to an increased adrenergic as well as dopaminergic transmission, no clear-cut evidence exists on whether one of these two neuronal systems mediates the behavioral effects of the tricyclic compound. Because a large body of evidence favors the role of dopamine, the interference of a selective inhibition of D1 or D2/D3 dopamine receptors on IMI effect upon the learned helplessness behavior (LH) in rats was studied. A 2-week treatment with SCH 23390, followed by a 24-h washout, showed almost the same efficacy as chronic IMI in preventing LH induction. Moreover, SCH 23390 given acutely before the pretest completely antagonized the effect of chronic IMI. Furthermore, SKF 38393 administered to drug-naive animals prior to the unavoidable shocks completely neutralized its behavioral sequelae. Finally, the inhibition of D2/D3 dopamine receptors by acute sulpiride did not modify IMI efficacy. These results strongly suggest that D1 dopamine receptor function controls the reactivity of animals exposed to a prolonged unavoidable stress, and mediates IMI antidepressant effect.
尽管慢性丙咪嗪（IMI）治疗的神经化学效应与肾上腺素能及多巴胺能传递增加有关，但关于这两个神经元系统中的哪一个介导了三环类化合物的行为效应，尚无明确证据。由于大量证据支持多巴胺的作用，因此研究了选择性抑制D1或D2/D3多巴胺受体对IMI对大鼠习得性无助行为（LH）影响的干扰作用。用SCH 23390进行为期2周的治疗，随后停药24小时，在预防LH诱导方面显示出与慢性IMI几乎相同的疗效。此外，在预测试前急性给予SCH 23390完全拮抗了慢性IMI的作用。此外，在不可避免的电击前给未用药的动物施用SKF 38393完全消除了其行为后遗症。最后，急性舒必利对D2/D3多巴胺受体的抑制并未改变IMI的疗效。这些结果强烈表明，D1多巴胺受体功能控制着暴露于长期不可避免应激的动物的反应性，并介导IMI的抗抑郁作用。
