Clozapine discrimination with a low training dose distinguishes atypical from typical antipsychotic drugs in rats.
BACKGROUND
Previous drug discrimination studies with clozapine have not reliably distinguished between atypical and typical antipsychotics.


OBJECTIVE
The present study was conducted to determine whether low-dose clozapine drug discrimination could distinguish atypical from typical antipsychotics.


METHODS
Rats were trained to discriminate 1.25 mg/kg clozapine from vehicle in a two-lever drug discrimination procedure.


RESULTS
Generalization testing revealed full substitution with the atypical antipsychotics olanzapine (90.3% maximum generalization), sertindole (99.8%), and risperidone (87.1%) and partial substitution for quetiapine (seroquel, 66.4%) and the typical antipsychotics haloperidol (56.8%) and thioridazine (74.3%). Remoxipride (23.1%) and the typical antipsychotics chlorpromazine (27.9%) and fluphenazine (29.5%) did not reliably substitute for clozapine.


CONCLUSIONS
In contrast to previous clozapine drug discrimination studies with higher training doses, the atypical antipsychotics olanzapine, sertindole, and risperidone reliably substituted for clozapine while typical antipsychotics did not. These results suggest that low-dose clozapine drug discrimination may be a more sensitive assay for distinguishing atypical from typical antipsychotic drugs.
Porter
J H
JH
Department of Psychology, Virginia Commonwealth University, Richmond 23284-2018, USA. jporter@vcu.edu
Varvel
S A
SA
Vann
R E
RE
Philibin
S D
SD
Wise
L E
LE
D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001569:Benzodiazepines; D003024:Clozapine / Q000008:administration & dosage / Q000494:pharmacology*; D004193:Discrimination Learning; D007093:Imidazoles / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D008297:Male; D000077152:Olanzapine; D010890:Pirenzepine / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018967:Risperidone / Q000494:pharmacology
D014150:Antipsychotic Agents; D007093:Imidazoles; D007211:Indoles; D001569:Benzodiazepines; D010890:Pirenzepine; C066304:sertindole; D003024:Clozapine; D018967:Risperidone; D000077152:Olanzapine