Trifunović R D, Brodie M S
Department of Physiology and Biophysics, University of Illinois at Chicago, College of Medicine, USA.
J Pharmacol Exp Ther. 1996 Jan;276(1):34-40.
Dopaminergic neurons of the ventral tegmental area (VTA) are important in the mediation of the rewarding properties of drugs of abuse such as ethanol. We have demonstrated in electrophysiological experiments in brain slices that serotonin potentiates the excitatory effect of ethanol on putative dopaminergic neurons of the VTA. Inasmuch as serotonin reuptake inhibitors have been shown to reduce ethanol intake in clinical studies, we investigated the effect of two serotonin reuptake inhibitors, clomipramine and zimelidine, on ethanol-induced excitation of VTA neurons recorded in vitro. Although zimelidine did potentiate ethanol-induced excitation in some neurons, on average, the effect of zimelidine was not significant. Significant potentiation of ethanol excitation was seen with 500 nM clomipramine, but not at higher or lower concentrations. In addition, clomipramine also enhanced the potentiation produced by low concentrations of serotonin. The lack of potentiation of ethanol excitation seen with application of higher concentrations of clomipramine could not be explained by inhibition of reuptake of norepinephrine or dopamine, and is probably due to blockade of 5-HT2 receptors by these higher concentrations of clomipramine. These results may have some implications for the development of serotonergic drugs, including serotonin uptake inhibitors, for the treatment of alcoholism.
腹侧被盖区（VTA）的多巴胺能神经元在介导诸如乙醇等滥用药物的奖赏特性方面很重要。我们已经在脑片的电生理实验中证明，5-羟色胺可增强乙醇对VTA假定多巴胺能神经元的兴奋作用。鉴于在临床研究中已表明5-羟色胺再摄取抑制剂可减少乙醇摄入量，我们研究了两种5-羟色胺再摄取抑制剂氯米帕明和齐美利定对体外记录的VTA神经元乙醇诱导兴奋的影响。尽管齐美利定在某些神经元中确实增强了乙醇诱导的兴奋作用，但总体而言，齐美利定的作用并不显著。500 nM氯米帕明可显著增强乙醇兴奋作用，但在更高或更低浓度时则不然。此外，氯米帕明还增强了低浓度5-羟色胺产生的增强作用。应用更高浓度氯米帕明时乙醇兴奋作用缺乏增强，这不能用去甲肾上腺素或多巴胺再摄取抑制来解释，可能是由于这些更高浓度的氯米帕明阻断了5-HT2受体。这些结果可能对开发用于治疗酒精中毒的5-羟色胺能药物（包括5-羟色胺摄取抑制剂）有一定启示。
