ANTAGONISM BY SCH-23390 OF CLOZAPINE-INDUCED HYPOTHERMIA IN THE RAT

Clozapine (7.5-30.0 mu mol kg(-1) s.c.) produced a decrease in core temperature in the rat. The temperature decrease caused by clozapine (7.5 mu mol kg(-1) s.c.) was fully antagonized by the selective dopamine D-1 receptor antagonist SCH 23390 (0.3 mu mol kg(-1)) s.c.), and a partial antagonism was obtained by the selective dopamine D-2 receptor antagonist raclopride (1.6 mu mol kg(-1) s.c.). On the other hand, the hypothermia was not antagonized by alpha-adrenoceptor antagonists (idazoxan and prazosin), 5-HT receptor antagonists ((-)-pindolol and ritanserin) or by the muscarinic M, receptor antagonist scopolamine. The hyperthermia produced by the 5-HT1C/2 receptor agonist DOI(0.75 mu mol kg(-1)) was blocked by clozapine (3.0 mu mol kg(-1) s.c.). Clozapine did not antagonize hypothermia produced by selective dopamine D-1 and D-2 receptor agonists (A 68930 and quinpirole), the alpha(2)-adrenoceptor agonist clonidine, the 5-HT1A receptor agonist 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin) or the muscarinic M(1) receptor agonist oxotremorine. The present results suggest that clozapine may be a partial agonist at brain dopamine D-1 receptors.