Dopamine and melatonin in the nucleus accumbens may be implicated in the mode of action of antidepressant drugs

The effect of chronic systemic treatment (once a day for 2–3 weeks) with different antidepressant drugs (desipramine, mianserin, fluvoxamine 15 mg/kg per day i.p. or s.c.) on the behavioral responses elicited by intra-accumbens injection of graded doses (1–10 000 ng) of apomorphine and two doses (10 and 100 ng) of melatonin was investigated in rats. Treatment with antidepressant drugs consistently facilitated apomorphine-induced hypermotility, but differentially influenced apomorphine-induced hypomotility. The drugs completely antagonized melatonin-induced behavioral changes (hypomotility and increased duration of sniffing). The data suggest that chronic treatment with antidepressant drugs results in postsynaptic dopamine receptor supersensitivity in the nucleus accumbens, a terminal area of the mesolimbic dopaminergic system. It is postulated that the development of supersensitivity may be mediated by the inhibition of melatonin-induced effects observed after acute and chronic treatment with these antidepressants. The present findings may be relevant for the mode of therapeutic action of antidepressant drugs.