Testosterone as well as estrogen increases serotonin 2A receptor mRNA and binding site densities in the male rat brain

Abstract

Our previous findings in female rats suggest that the potent effects of sex steroids on mood and mental state may be mediated, in part, by the effect of estrogen on the 5-hydroxytryptamine 2A receptor (5-HT 2AR) in brain. The aim of the present study was to determine the effect of acute (∼32h) sex steroid manipulation on central 5-HT 2AR in the adult male Wistar rat. Castration (under halothane anesthesia) decreased while testosterone or estrogen, but not 5α-dihydrotestosterone (5α-DHT), increased significantly the 5-HT 2AR mRNA content in dorsal raphe nucleus and the density of 5-HT 2AR binding sites in frontal, cingulate and primary olfactory cortex and nucleus accumbens. The lack of effect of 5α-DHT, a potent androgen which cannot be converted to estrogen, suggests that the action of testosterone depends upon its conversion to estrogen by aromatase. This may also explain why estrogen, but not testosterone or 5α-DHT, increased the density of 5-HT 2AR binding sites in the caudate-putamen, a brain region where aromatase is scarce. These findings are discussed in relation to the possible role of the 5-HT 2AR in depression, schizophrenia and Alzheimer's Disease.