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Abstract:
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The mechanism by which the atypical neuroleptic clozapine is able to relieve the symptoms of schizophrenia without causing extrapyramidal side effects that are characteristic of most other antipsychotic drugs is unclear. c-fos is a proto-oncogene that encodes a 55 kDa phosphoprotein, Fos, which is thought to be an activity marker in the central nervous system. Recently, it has been shown that clozapine and haloperidol produce distinct patterns of increased c-fos expression in the rat forebrain. Haloperidol induces Fos-like immunoreactivity (FLI) in the nucleus accumbens, dorsolateral striatum and lateral septal nucleus, whereas clozapine preferentially increases in FLI in limbic structures such as the prefrontal cortex, nucleus accumbens, mediolateral striatum and lateral septal nucleus. These findings suggest that clozapine's unique therapeutic profile may be related to its failure to induce FLI in the striatum as well as its idiosyncratic actions in the medial prefrontal cortex. Given the significant clinical implications of these results, the present study attempted to identify these receptors which mediate the different effects of clozapine and haloperidol on c-fos expression. (Abstract shortened by UMI.) |
