mRNAs for clozapine-sensitive receptors co-localize in rat prefrontal cortex neurons

The clinical efficacy of clozapine in treating schizophrenia may Stem from its lack of receptor selectivity. If true, several clozapine-sensitive receptors may be co-expressed by neurons dysfunctional in schizophrenia. To test this hypothesis, neurons from the rat medial prefrontal cortex were acutely isolated and subjected to single cell RT-PCR analysis. The co- ordinated expression of five clozapine-sensitive receptors (D₄, ml, 5- HT(2a), 5-HT(2c), 5-HT₇) was examined in interneurons and pyramidal neurons. Profiling of GABAergic interneurons commonly revealed the co-expression of two or more clozapine-sensitive receptor mRNAs. Although co-expression of these receptors was less extensive in pyramidal neurons, it was also commonly found. These results suggest that clozapine's therapeutic effects may be mediated by antagonism of dopaminergic, cholinergic and serotoninergic signaling pathways at the single cell level.