The discriminative stimulus properties of the atypical antipsychotic olanzapine in rats

Citation
Jh. Porter et al., The discriminative stimulus properties of the atypical antipsychotic olanzapine in rats, PSYCHOPHAR, 148(3), 2000, pp. 224-233
Citations number
59
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Neurosciences & Behavoir
Journal title
Volume
148
Issue
3
Year of publication
2000
Pages
224 - 233
Database
ISI
SICI code
Abstract
Rationale: Analysis of the preclinical behavioral effects of atypical antip sychotic agents will provide a better understanding of how they differ from typical. antipsychotics and aid in the development of future atypical anti psychotic drugs. Objectives: The present study was designed to provide info rmation about the discriminative stimulus properties of the atypical antips ychotic olanzapine. Methods: Rats were trained to discriminate the atypical antipsychotic olanzapine (either 0.5 mg/kg OLZ or 0.25 mg/kg OLZ, i.p.) fr om vehicle in a two-lever drug discrimination procedure. The atypical antip sychotic clozapine fully substituted for olanzapine in both the 0.5-mg/kg O LZ group (99.3% drug lever responding [DLR]) and the 0.25-mg/kg OLZ group ( 99.9% DLR). The typical antipsychotic chlorpromazine also substituted for o lanzapine in both the 0.5-mg/kg OLZ group (87.5% DLR) and in the 0.25-mg/kg OLZ group (98.9% DLR; whereas, haloperidol displayed partial substitution for olanzapine in the 0.5-mg/kg OLZ group (56.1% DLR) and in the 0.25-mg/kg OLZ group (76.4% DLR). The 5.0-mg/kg dose of thioridazine produced olanzap ine-appropriate responding in the 0.5-mg/kg OLZ group (99.6% DLR), but only partial substitution was seen with the 0.25-mg/kg OLZ training dose (64.0% DLR). The atypical antipsychotics raclopride (53.9% DLR) and risperidone ( 60.1% DLR) displayed only partial substitution in the 0.5-mg/kg OLZ group. Both the muscarinic cholinergic antagonist scopolamine (90.0% DLR) and the. 5-HT2A/2C serotonergic antagonist ritanserin (86.0% DLR) fully substituted for olanzapine in the 0.5-mg/kg OLZ group. Conclusions: In contrast to pre vious discrimination studies with clozapine-trained rats, the typical antip sychotic agents chlorpromazine and thioridazine and the serotonin antagonis t ritanserin substituted for olanzapine. These results demonstrate that the re are differences in the mechanisms underlying the discriminative stimulus properties of clozapine and olanzapine. Specifically, olanzapine's discrim inative stimulus properties appear to be meditated in part by both choliner gic and serotonergic mechanisms.