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Role of D 1 and D 2 dopamine receptors in the discriminative stimulus properties of the atypical antipsychotic clozapine in rats
Author(s) -
Porter Joseph H.,
Villanueva Heidi F.,
Rosecrans John A.
Publication year - 1999
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/(sici)1098-2299(199902)46:2<139::aid-ddr7>3.0.co;2-s
Subject(s) - clozapine , haloperidol , dopamine receptor d2 , pharmacology , antipsychotic , dopamine , atypical antipsychotic , dopamine antagonist , antipsychotic agent , dopamine receptor , typical antipsychotic , antagonist , psychology , medicine , receptor , schizophrenia (object oriented programming) , psychiatry
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 clozapine‐appropriate 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. Drug Dev. Res. 46:139–147, 1999. © 1999 Wiley‐Liss, Inc.