Regional differences in the action of antipsychotic drugs: implications for cognitive effects in schizophrenic patients

Abstract

Antipsychotic drugs (APDs) have been classified as typical or atypical based on their liability to produce extrapyramidal side effects: atypical APDs are less likely to produce extrapyamidal side effects at therapeutic doses. Evidence from immediate early gene immunohistochemical, electrophysiological, microdialysis, imaging, and behavioral studies suggests that typical APDs preferentially affect the nucleus accumbens (NAc) and the dorsal striatum while atypical APDs preferentially affect the NAc and medial prefrontal cortex (PFC). We review some of this evidence and then discuss studies that have employed cognitive tasks shown previously to depend on dorsal striatal or medial PFC function in schizophrenic patients treated with typical or atypical APDs. Results revealed that patients treated with typical APDs displayed deficits in cognitive tasks that depended on the dorsal striatum but not in tasks that depended on the medial PFC and that those treated with atypical APDs displayed deficits in cognitive tasks that depended on the medial PFC but not in cognitive tasks that depended on the dorsal striatum. These findings suggest that some of the cognitive deficits seen in schizophrenic patients may be related to the medications that are used to treat them.