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.
Durlach-Misteli
C
C
Department of Pharmacology, Rudolf Magnus Institute, Medical Faculty, University of Utrecht, Netherlands.
Van Ree
J M
JM
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001058:Apomorphine / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D003891:Desipramine / Q000494:pharmacology; D004298:Dopamine / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D016666:Fluvoxamine / Q000494:pharmacology; D008297:Male; D008550:Melatonin / Q000494:pharmacology / Q000502:physiology*; D008803:Mianserin / Q000494:pharmacology; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D011954:Receptors, Dopamine / Q000187:drug effects / Q000502:physiology; D012680:Sensitivity and Specificity
D000928:Antidepressive Agents; D014179:Neurotransmitter Uptake Inhibitors; D011954:Receptors, Dopamine; D008803:Mianserin; D008550:Melatonin; D001058:Apomorphine; D016666:Fluvoxamine; D003891:Desipramine; D004298:Dopamine