Estrogen increases the density of 5-hydroxytryptamine(2A) receptors in cerebral cortex and nucleus accumbens in the female rat.

Estrogen exerts a profound effect on mood and mental function in man. Based on our finding that estradiol selectively stimulates the expression of 5-hydroxytryptamine(2A) (5-HT2A) receptor mRNA in the dorsal raphe nucleus of the female rat, we investigated the effects of estradiol on the density of 5-HT2A receptors in brain. The distribution and density of 5-HT2A receptors were determined by in vitro binding of [3H]ketanserin in the presence of prazosin to exclude binding to alpha 1-adrenoreceptors. Brains were collected, processed and analysed in pairs from six estradiol- and six vehicle-treated animals. Our results show that a single pulse of estradiol induces a significant increase in the density of 5-HT2A receptors in female rat forebrain, particularly the anterior frontal, anterior cingulate and primary olfactory cortex and the nucleus accumbens. Since these brain regions play a pivotal role in cognition and emotion, as well as neuroendocrine and motor control, our findings provide the first experimental evidence for the fact that estrogen could alter mood and mental state by increasing the density of 5-HT2A receptors in cerebral cortex and nucleus accumbens.