Role of D1 and D2 dopamine receptors in the discriminative stimulus properties of the atypical antipsychotic clozapine in rats

✍ Scribed by Joseph H. Porter; Heidi F. Villanueva; John A. Rosecrans

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 139 KB
• Volume: 46
• Category: Article
• ISSN: 0272-4391
• DOI: 10.1002/(sici)1098-2299(199902)46:2<139::aid-ddr7>3.0.co;2-s

✦ Synopsis

The purpose of the present study was to assess the role of dopamine D 1 and D 2 receptors in the discriminative stimulus properties of the atypical antipsychotic clozapine (CLZ). Two groups of rats were trained to discriminate either a moderate dose of clozapine (5.0 mg/kg) from vehicle or a high dose of clozapine (10.0 mg/kg) from vehicle in a two-lever drug discrimination paradigm. Generalization testing with clozapine yielded an ED 50 of 0.9 mg/kg (95% confidence limits = 0.5-2.0 mg/kg) for the 5.0 CLZ group and 2.0 mg/kg (95% confidence limits = 1.4-2.8 mg/kg) for the 10.0 CLZ group. Substitution testing with the D 1 antagonist SCH 23390 and the D 2 dopamine antagonist haloperidol failed to produce clozapineappropriate responding for either of the clozapine training doses. The antipsychotic drug thioridazine (which binds to a number of neurotransmitters in addition to dopamine) produced partial substitution (64.5% drug lever responding) in the 5.0 CLZ group at the 5.0 mg/kg dose. These results suggest that antagonism of D 1 and D 2 dopamine receptors alone is not sufficient to produce clozapine-appropriate responding, even with the higher training dose of 10.0 mg/kg.