INTERACTIONS OF CLOZAPINE WITH THE STIMULUS EFFECTS OF DOM AND LSD

Two groups of rats were trained with the 5-HT2 agonists 2,5-dimethoxy- 4-methylamphetamine (DOM) or lysergic acid diethylamide (LSD) in a two -lever discrimination task. Tests of generalization and antagonism wer e then carried out with clozapine. DOM did not generalize to clozapine . Partial antagonism of DOM was observed with 0.3, 1, and 2 mg/kg cloz apine and statistically significant full antagonism with 3 mg/kg. LSD did not fully generalize to clozapine. Partial antagonism of LSD was o bserved with 3 and 4 mg/kg clozapine. Because clozapine is known to bl ock muscarinic as well as 5-HT2 receptors, atropine was studied in DOM -trained rats. DOM partially generalized to 3 mg/kg atropine. Partial attenuation of DOM stimulus effects was observed with 3 mg/kg atropine , and no attenuation with 5 mg/kg. A combination of 2 mg/kg clozapine and 3 mg/kg atropine vs. DOM produced response suppression in five of seven rats. The atropine test results do not exclude the possibility o f an antimuscarinic component in the observed attenuation of DOM and L SD stimulus effects by clozapine.