Testosterone as well as estrogen increases serotonin2A receptor mRNA and binding site densities in the male rat brain

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-HT2AR) in brain. The aim of the present study was to determine the effect of acute (similar to 32h) sex steroid manipulation on central 5-HT2AR in the adult male Wistar rat. Castration (under halothane anesthesia) decreased while testosterone or estrogen, but not 5 alpha-dihydrotestosterone (5 alpha-DHT), increased significantly the 5-HT2AR mRNA content in dorsal raphe nucleus and the density of 5-HT2AR binding sites in frontal, cingulate and primary olfactory cortex and nucleus accumbens. The lack of effect of 5 alpha-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 5 alpha-DHT, increased the density of 5-HT2AR 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-HT2AR in depression, schizophrenia and Alzheimer's Disease. (C) 1998 Elsevier Science B.V. All rights reserved.