The cataleptogenic effects of the neuroleptic nemonapride are attenuated by its 5-HT_1A receptor agonist properties

The effects of the 5-HT_1A receptor antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)- cyclohexanecarboxamide (WAY 100635) on catalepsy induced by the dopamine D₂-like receptor antagonist/5-HT_1A receptor agonist nemonapride were examined and compared to its effects on catalepsy induced by neuroleptics that have low affinity for 5-HT_1A receptors. Nemonapride induced catalepsy in both cross-legged position and bar tests at low, but not at high doses. Pretreatment with WAY 100635 (0.63 mg/kg) reinstated catalepsy at higher doses of nemonapride, indicating that the 5-HT_1A receptor agonist properties of nemonapride are responsible for its inability to produce catalepsy at high doses. Additionally, WAY 100635 enhanced significantly the effects of low doses of nemonapride, and of the dopamine D₂-like receptor antagonists raclopride and haloperidol. The present data indicate that the 5-HT_1A receptor agonist properties of nemonapride attenuate its ability to induce catalepsy at higher doses, and suggest further that tonic 5-HT_1A receptor activation may modulate neuroleptic-induced catalepsy.