Serotonergic mechanisms in neuroleptic-induced catalepsy in the rat

The present paper reviews a series of experiments aimed at elucidating the interaction between specific dopamine (DA) and 5-hydroxytryptamine (5-HT) receptors in the mediation of extrapyramidal motor functions in the rat. There is strong evidence to suggest that (1) the catalepsy produced by dopamine D-1 or D-2 receptor antagonists can be completely antagonized by the administration of 5-HT1A receptor agonists acting at 5-HT autoreceptors in the median raphe nucleus; (2) the catalepsy produced by a dopamine D-2 receptor antagonist can be completely antagonized by treatment with a 5-HT2A/C receptor agonist; and (3) the catalepsy produced by blockade of either dopamine D-1 or D-2 receptors is not affected by the administration of a 5-HT2A/C receptor antagonist. The emerging picture of DA/5-HT receptor interactions in the mediation of extrapyramidal motor functions is of great interest in relation to present efforts to develop new atypical neuroleptics with affinity for brain 5-HT receptor subtypes, and also for the observations that new serotonin selective re-uptake inhibiting antidepressants can produce parkinson-like symptoms in vulnerable individuals. Copyright (C) 1996 Elsevier Science Ltd.