EFFECTS OF ANTIPSYCHOTICS ON COGNITIVE-BEHAVIOR IN RATS USING THE DELAYED NON-MATCH TO POSITION PARADIGM

The acute effects of the dopamine D-1 receptor antagonist SCH 23390 [(R)-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepin-7-ol] hemimaleat, the dopamine D-2 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 D-1 and D-2 receptor antagonists, respectively, were associated with the dominance of dopamine D-1 receptors in the prefrontal cortex and of dopamine D-2 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.