Supersensitivity to L-5-hydroxytryptophan after 5,7-dihydroxytryptamine injections in desmethylimipramine- and nomifensine-pretreated rats: behavioral evidence for postsynaptic supersensitivity.

The behavioral syndrome induced by L-5-hydroxytryptophan (L-5-HTP) in rats was used to study the supersensitivity to L-5-HTP and 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) which develops after unilateral intracerebroventricular (ICV) injections of 200 microgram 5,7-dihydroxytryptamine (5,7-DHT). Pretreatment of the animals with a combination of desipramine and nomifensine was found to protect dopamine neurones better than desipramine alone. Maximal behavioral supersensitivity to L-5-HTP and 5-MeODMT was found as early as 24 h after injection of the neurotoxin, even in the presence of the specific 5-HT uptake inhibitor CGP 6085 A, or the MAO-A inhibitor clorgyline. The results indicate that a quickly occurring postsynaptic event contributes to the development of behavioral supersensitivity after ICV injections of 5,7-DHT.