Reduction of oral ethanol self-administration in rats by monoamine oxidaseinhibitors

Evidence for a role of dopamine and serotonin in the control of ethanol int ake in animals suggests that monoamine oxidase (MAO) inhibitors, which incr ease the synaptic availability of serotonin and dopamine by blocking their metabolism, might have efficacy in the treatment of alcohol dependence. The aim of the present study was, therefore, to evaluate several MAO inhibitor s for their capacity to affect ethanol self-administration in rats trained to self-administer ethanol (10% v/v) orally in a free-choice two-lever oper ant task. The nonselective and irreversible MAO inhibitors, phenelzine (3-1 0 mg/kg), tranylcypromine (1-3 mg/kg), and nialamide (30 mg/kg), decreased rates of responding maintained by ethanol reinforcement. The reversible MAO -A inhibitor, befloxatone (0.3-3 mg/kg), and the irreversible MAO-A inhibit or, clorgyline (10-30 mg/kg), also reduced ethanol self-administration Howe ver, befloxatone-induced effects leveled off at a 50% decrease. The irrever sible MAO-B inhibitors, pargyline (30 mg/kg) and I-deprenyl (3-10 mg/kg) al so decreased responding maintained by ethanol reinforcement; these results are consistent with previous findings that both drugs decreased ethanol int ake in mice. In conclusion, the present results showing that several MAO in hibitors decreased ethanol self-administration in rats are consistent with previous findings that synaptic levels of serotonin and dopamine play a cri tical role in the control of ethanol self-administration. (C) 1999 Elsevier Science Inc.