Effects of antipsychotics on cognitive behaviour in rats using the delayed non-match to position paradigm.
The acute effects of the dopamine D1 receptor antagonist SCH 23390 [(R)-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepi n-7-ol d hemimaleat, the dopamine D2 receptor antagonists raclopride and haloperidol, the compounds with mixed receptor profiles clozapine, risperidone and sertindole, the alpha 1-adrenoceptor antagonist prazosin and scopolamine were investigated in a delay-response task, a test for working memory, for rats. SCH 23390 induced a delay-dependent impairment of the performance. Raclopride, haloperidol, clozapine, and risperidone induced a delay-independent impairment. Sertindole was without effect. The specific (delay-dependent) and unspecific (delay-independent) effects on working memory of the dopamine D1 and D2 receptor antagonists, respectively, were associated with the dominance of dopamine D1 receptors in the prefrontal cortex and of dopamine D2 receptors in the basal structures of the brain. Prazosin did not affect working memory; however, a reduction in intertrial responses was found. Scopolamine induced a delay-independent impairment. It is concluded that the compounds have different activity profiles in this cognitive task. This finding may have important implications for the development of antipsychotics with a lower propensity for cognitive side effects.
Department of Psychopharmacology, St. Hans Hospital, Roskilde, Denmark.
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Didriksen
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D001552:Benzazepines / Q000494:pharmacology*; D003024:Clozapine / Q000494:pharmacology; D003071:Cognition / Q000187:drug effects*; D018492:Dopamine Antagonists / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D008568:Memory / Q000187:drug effects*; D020891:Raclopride; D051381:Rats; D017208:Rats, Wistar; D012457:Salicylamides / Q000494:pharmacology*; D013997:Time Factors
D014150:Antipsychotic Agents; D001552:Benzazepines; D018492:Dopamine Antagonists; D012457:Salicylamides; D020891:Raclopride; D003024:Clozapine; D006220:Haloperidol