THE CATALEPTOGENIC EFFECTS OF THE NEUROLEPTIC NEMONAPRIDE ARE ATTENUATED BY ITS 5-HT1A RECEPTOR AGONIST PROPERTIES

The effects of the 5-HT1A receptor antagonist zinyl]ethyl]-N-(2-pyridi nyl)-cyclhexanecarboxamide (WAY 100635) on catalepsy induced by the do pamine D-2-like receptor antagonist/5-HT1A receptor agonist nemonaprid e were examined and compared to its effects on catalepsy induced by ne uroleptics that have low affinity for 5-HT1A receptors. Nemonapride in duced catalepsy in both cross-legged position and bar tests at low, bu t not at high doses. Pretreatment with WAY 100635 (0.63 mg/kg) reinsta ted 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 o f the dopamine D-2-like receptor antagonists raclopride and haloperido l. The present data indicate that the 5-HT1A receptor agonist properti es of nemonapride attenuate its ability to induce catalepsy at higher doses, and suggest further that tonic 5-HT1A receptor activation may m odulate neuroleptic-induced catalepsy. (C) 1998 Elsevier Science B.V. All rights reserved.