Gonadal hormones modulate 5-hydroxytryptamine2A receptors: emphasis on the rat frontal cortex

The effect of short-term (Sprague-Dawley rats, two weeks) and long-term ovariectomy (Sprague-Dawley and Fischer rats, three months) on serotonin 5-hydroxytryptamine2A receptors in different regions of the brain and its possible correction with an 17 beta-estradiol treatment (10 micrograms, b.i.d., two weeks) were studied in comparison to intact rats. Saturation binding assays were performed using [3H]ketanserin to estimate 5-hydroxytryptamine2A receptor density and affinity in tissue homogenates of frontal cortex of Fischer rats and quantitative autoradiography was performed to evaluate receptor specific binding in frontoparietal cortex, nucleus accumbens, striatum and dorsal raphe nucleus of Fischer rats, and in frontal cortex of the two strains of rats. Messenger RNA levels of 5-hydroxytryptamine2A receptors were measured by in situ hybridization in frontal cortex of the two strains of rats. An overall decrease of 5-hydroxytryptamine2A receptor densities was found in all the brain regions of ovariectomized Fischer rats assayed, and this could be restored towards control levels by estradiol treatment. No change in the 5-hydroxytryptamine2A receptor affinity was measured in the frontal cortex. A similar pattern of changes was observed for the messenger RNA levels encoding the 5-hydroxytryptamine2A receptors and receptor density, suggesting the implication of a genomic mechanism. Experiments in Sprague-Dawley rats confirmed and extended the results obtained with Fischer rats. By analogy, in humans, this 5-hydroxytryptamine2A receptor modulation may underlie the mood and movement disorders associated with menopause.