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 rece ptors may be co-expressed by neurons dysfunctional in schizophrenia. To tes t this hypothesis, neurons from the rat medial prefrontal cortex were acute ly isolated and subjected to single cell RT-PCR analysis. The cc-ordinated expression of five clozapine-sensitive receptors (D-4, m1, 5-HT2a, 5-HT2c, 5-HT7) was examined in interneurons and pyramidal neurons. Profiling of GAB Aergic interneurons commonly revealed the co-expression of two or more cloz apine-sensitive receptor mRNAs. Although co-expression of these receptors w as less extensive in pyramidal neurons, it was also commonly found. These r esults suggest that clozapine's therapeutic effects may be mediated by anta gonism of dopaminergic, cholinergic and serotoninergic signaling pathways a t the single cell level. (C) 1998 Published by Elsevier Science Ireland Ltd . All rights reserved.