title: Differential effects of nialamide and clomipramine on serotonin efflux and autoreceptors.
abstract: Serotonin (5-HT) activity in vivo and in vitro was evaluated in rats following acute and chronic administration of the antidepressants nialamide (NMD) and clomipramine (CMI). The 5-HT motor syndrome was used as an index of in vivo serotonergic function. In vitro, 3H-5-HT uptake, potassium-evoked 3H-5-HT release and 5-HT autoreceptor activity were evaluated as measures of presynaptic function. Repeated injections of NMD abolished the 5-methoxy-N, N-dimethyltryptamine (5-MeODMT)-induced motor syndrome and the ability of 5-methoxytryptamine (5-MEOT) to attenuate the potassium-evoked release of 3H-5HT. Autoreceptor subsensitivity was associated with a marked increase in basal and potassium-evoked 3H-5-HT release. In contrast, acute NMD, and acute and chronic CMI did not affect the expression of the motor syndrome or alter 3H-HT release or autoreceptor activity. Acute and chronic injections of NMD enhanced 3H-5-HT uptake. The results suggest that the antidepressant efficacy of monoamine oxidase inhibitor (MAOI) antidepressants may be related to their ability to increase endogenous levels of 5-HT and thereby produce a subsensitivity of 5-HT1 type receptors. This subsensitivity is reflected both by attenuation of the motor syndrome and enhanced 5-HT neurotransmission resulting in part from autoreceptor down-regulation.
mesh_terms: D008735:5-Methoxytryptamine / Q000494:pharmacology; D000818:Animals; D002997:Clomipramine / Q000494:pharmacology*; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D009526:Nialamide / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects*; D012701:Serotonin / Q000378:metabolism*; D013239:Stereotyped Behavior / Q000187:drug effects
chemical_list: D011985:Receptors, Serotonin; D012701:Serotonin; D008735:5-Methoxytryptamine; D006897:Hydroxyindoleacetic Acid; D002997:Clomipramine; D009526:Nialamide