SEROTONIN-2/1C RECEPTOR ACTIVATION CAUSES A LOCALIZED EXPRESSION OF THE IMMEDIATE-EARLY GENE C-FOS IN RAT-BRAIN - EVIDENCE FOR INVOLVEMENT OF DORSAL RAPHE NUCLEUS PROJECTION FIBERS

Immunocytochemistry has been used to monitor the expression of the immediate-early gene c-fos in rat brain following administration of the serotonin2/1C receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane. At parenteral doses of 2 or 8mg/kg the drug caused a highly localized expression of the Fos protein in frontal, parietal, cingulate and piriform cortex as well as in claustrum, mamillary bodies, globus pallidus, amygdala, nucleus accumbens and dorsomedial striatum. In particular, the location of heavy Fos immunoreactivity in the primary somatosensory cortex corresponds precisely to that region (layer Va) shown in other reports to receive a dense input of fine, non-varicose fibres which may arise from the dorsal raphe nucleus. All of the Fos-positive brain regions in the present study have been previously demonstrated to contain serotonin, receptor ligand binding sites. Interestingly, no Fos-positive cells were found in the hippocampus, another brain region known to contain serotonin2 receptors. Pretreatment of animals with the serotonin2/1C receptor antagonist ritanserin (0.4mg/kg) markedly attenuated Fos expression in all reactive areas of the brain. Counts of reactive cells indicated that this antagonism of the Fos response was statistically significant in these brain regions. Spiperone (1 mg/kg), a mixed serotonin2 and dopamine D2 antagonist, also attenuated the Fos response in the same regions, but had the effect of inducing Fos expression on its own in other extrapyramidal brain regions. Double labelling of reactive cells with different antisera recognizing Fos and neuron-specific enolase, and lack of double labelling with a glial fibrillary acidic protein antiserum, indicated that the Fos expression was in neurons within the brain nuclei examined. The results indicate that the c-fos immunocytochemical technique is a valuable tool for studying the anatomy and pharmacology of serotonin receptors in experimental animal brain.