Generalization to atypical antipsychotic drugs depends on training dose in rats trained to discriminate 1.25 mg/kg clozapine versus 5.0 mg/kg clozapine versus vehicle in a three-choice drug discrimination task
In: Behavioural Pharmacology, Jg. 16 (2005-11-01), S. 511-520
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Zugriff:
The prototypical atypical antipsychotic drug (APD) clozapine (CLZ) elicits a discriminative cue that appears to be similar to the stimulus properties elicited by atypical, but not typical, antipsychotic drugs in two-choice drug discrimination procedures. However, the ability of CLZ to generalize to atypical APDs depends on the training dose, since several atypical APDs (e.g. sertindole, risperidone) do not substitute for a 5.0 mg/kg CLZ training dose in rats, but do so for a 1.25 mg/kg CLZ training dose. Yet, a 1.25 mg/kg CLZ discriminative stimulus has not generalized to all atypical APDs either (e.g. quetiapine); thus, both 1.25 mg/kg and 5.0 mg/kg CLZ discriminative stimuli may be necessary to provide a better screen for atypical APDs. The present study sought to determine whether a three-choice 1.25 mg/kg CLZ versus 5.0 mg/kg CLZ versus vehicle drug discrimination task in rats might better distinguish atypical from typical APDs. Adult male Sprague-Dawley rats were trained in this three-choice drug discrimination task with a fixed ratio 30 reinforcement schedule for food. Clozapine produced full substitution (≥ 80% condition-appropriate responding) for both the 1.25 mg/kg CLZ dose (ED 5 0 =0.09 mg/kg) and the 5.0 mg/kg CLZ dose (ED 5 0 =2.71 mg/kg). The atypical APD olanzapine produced full substitution for the 5.0 mg/kg CLZ dose, but not for the 1.25 mg/kg CLZ dose (ED 5 0 =1.55 mg/kg). In contrast, the atypical APD quetiapine produced full substitution for the 1.25 mg/kg CLZ dose (ED 5 0 =0.13 mg/kg), but not for the 5.0 mg/kg CLZ dose. Similarly, the atypical APD sertindole produced full substitution for only the 1.25mg/kg CLZ dose (ED 5 0 =0.94 mg/kg). Risperidone, another atypical APD, produced partial substitution (≥ 60% and ≤ 80% condition-appropriate responding) for the 1.25 mg/kg CLZ dose, and failed to substitute for the 5.0 mg/kg CLZ dose. The atypical APD ziprasidone and the typical APDs haloperidol and chlorpromazine failed to substitute for either CLZ training dose. These results demonstrated that the 1.25 mg/kg CLZ training dose provides partial or full stimulus generalization to more atypical APDs than does the 5.0 mg/kg CLZ training dose. Full substitution by olanzapine for only the 5.0 mg/kg CLZ dose suggests that this higher training dose is also important for screening atypical APDs.
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Generalization to atypical antipsychotic drugs depends on training dose in rats trained to discriminate 1.25 mg/kg clozapine versus 5.0 mg/kg clozapine versus vehicle in a three-choice drug discrimination task
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Autor/in / Beteiligte Person: | Pehrson, Alan L. ; Philibin, Scott D. ; Porter, Joseph H. ; Prus, Adam J. |
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Zeitschrift: | Behavioural Pharmacology, Jg. 16 (2005-11-01), S. 511-520 |
Veröffentlichung: | Ovid Technologies (Wolters Kluwer Health), 2005 |
Medientyp: | unknown |
ISSN: | 0955-8810 (print) |
DOI: | 10.1097/01.fbp.0000172735.73876.06 |
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