Genomic responses to 5-HT 1a or 5-HT 2a2c receptor activation is differentially regulated in four regions of rat brain

The functional profiles of brain 5-HT 1A and 5-HT 2Ac receptors were assessed by quantitating changes in the immediate early genes — c-fos, ngflc and tisl, following receptor activation with either 8-OH-DPAT (8-hydroxy-2-(di- n -propylamino)tetralin) or DOI (1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane). Stimulation of either class of 5-HT receptor elicited an induction of all three immediate early genes to varying extents in cortex, hippocampus and cerebellum, but not in striatum. The responses to 8-OH-DPAT peaked earlier than those to DOI. WAY 100135 ( N -tertiobutyl-3-[4-(2-methoxyphenyl)-piperazinyl]-2-phenylpropanamide), the putative 5-HT 1A receptor antagonist blocked the 8-OH-DPAT effect but not the responses to DOI. WAY 100135 by itself also elicited a relatively smaller genomic response. Ketanserin completely abolished the DOI-induced genomic responses. The results support the earlier findings that 5-HT 1A receptor sites are abundant in frontal cortex and hippocampus. In addition, the robust genomic responses to 8-OH-DPAT as well as Northern hybridization with a cDNA probe for 5-HT 1A mRNA in the cerebellum clearly implicate the functional expression of 5-HT 1A receptors in this brain region. The responses to the 5-HT 2 receptor agonist, DOI support a greater abundance of these receptors in the cortex, and relatively lower levels in hippocampus and cerebellum. The results suggest a differential induction pattern among the three immediate-early genes depending on the brain region and the 5-HT receptor subtype involved.