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 D1 or D2 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 D2 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 D1 or D2 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.