THE EFFECTS OF CLOMIPRAMINE ON THE EXCITATORY ACTION OF ETHANOL ON DOPAMINERGIC-NEURONS OF THE VENTRAL TEGMENTAL AREA IN-VITRO

Dopaminergic neurons of the ventral tegmental area (VTA) are important in the mediation of the rewarding properties of drugs of abuse such a s ethanol. We have demonstrated in electrophysiological experiments in brain slices that serotonin potentiates the excitatory effect elf eth anol on putative dopaminergic neurons of the VTA. inasmuch as serotoni n reuptake inhibitors have been shown to reduce ethanol intake in clin ical studies, we investigated the effect of two serotonin reuptake inh ibitors, clomipramine and zimelidine, on ethanol-induced excitation of VTA neurons recorded in vivo. Although zimelidine did potentiate etha nol-induced excitation in some neurons, on average, the effect of zime lidine was not significant. Significant potentiation of ethanol excita tion was seen with 500 nM clomipramine, but not at higher or lower con centrations. 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 o f clomipramine could not be explained by inhibition of reuptake of nor epinephrine or dopamine, and is probably due to blockade of 5-HT2 rece ptors by these higher concentrations of clomipramine. These results ma y have some implications for the development of serotonergic drugs, in cluding serotonin uptake inhibitors, for the treatment of alcoholism.