Effects of typical and atypical antipsychotic drugs on response decrement patterns in rats

DJ Sanger and G Perrault

Synthelabo Recherche, Bagneux, France.

Within-session decrements in instrumental responding are a characteristic effect of certain neuroleptic drugs including haloperidol and pimozide. There is little consensus, however, as to whether these effects can best be explained as motivational or motor deficits. A number of recently developed drugs have been described as atypical antipsychotics and are claimed to produce fewer motor side effects than more traditional neuroleptics. Little work has been done to investigate whether such atypical agents also give rise to within- session response decrements. The present experiment used the operant responding of rats to study the effects of a range of antipsychotic drugs. Rats were trained to lever press for food during daily sessions (FR10 schedule) and responding was recorded during each 3-min period of the 15-min sessions. Dose-related decreases in overall response rates were produced by all the drugs studied; ED50 values were: haloperidol 0.17 mg/kg, risperidone 0.18 mg/kg, setoperone 0.23 mg/kg, remoxipride 1.2 mg/kg, sertindole 4.8 mg/kg, thioridazine 7.6 mg/kg, clozapine 8.9 mg/kg, amisulpride 34 mg/kg, sulpiride 74 mg/kg. The presence of within- session response decrements was confirmed for haloperidol and demonstrated with remoxipride, but similar effects were not observed with clozapine, thioridazine, risperidone, sertindole, setoperone, sulpiride and amisulpride. As a number of these drugs were known to have high affinity for 5HT2 receptors, the effects of the 5HT2 antagonist ritanserin (1 and 10 mg/kg) were studied alone and in combination with haloperidol. Ritanserin had no effect on response rates, and did not antagonize but rather potentiated the effect of haloperidol.(ABSTRACT TRUNCATED AT 250 WORDS)

Volume 272, Issue 2, pp. 708-713, 02/01/1995
Copyright © 1995 by American Society for Pharmacology and Experimental Therapeutics

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