Effects of chronic 17 beta-estradiol treatment on the serotonin 5-HT1A receptor mRNA and binding levels in the rat brain

Acute 17 beta-estradiol treatment had been shown to downregulate the 5-HT1A receptor mRNA expression in limbic areas of the female rat brain. The aim of the present study was to determine the effects of chronic 17 beta-estrad iol treatment on 5-HT1A receptor mRNA expression and 5-HT1A receptor bindin g in ovariectomized female rats. Using in situ hybridization histochemistry , no alterations were found on the 5-HT1A receptor mRNA levels after the es tradiol treatment (2 weeks). Radioligand autoradiographic studies using the selective 5-HT1A receptor antagonist [H-3]WAY-100635 revealed reduced rece ptor binding in the amygdala, hippocampus, perirhinal cortex, and motor cor tex after estradiol treatment, whereas no changes were observed in the piri form or retrosplenial cortex. Thus, the previous findings together with the present results indicate that estradiol-induced alterations in 5-HT1A rece ptor mRNA expression appears within hours, but diminishes with chronic trea tment when significant changes on the receptor-protein level are apparent. The effects of estradiol treatment on the 5-HT1A receptor binding in the li mbic areas suggest that estrogen can modulate functions such as learning, m emory, cognition, emotional processing, and social behavior. Consequently, estradiol modulation of 5-HT1A receptor circuits might be a possible pathwa y for the estrogen influence in the expression of psychiatric and neurologi cal disorders such as Alzheimer's disease, affective disorders, and schizop hrenia. Synapse 35:39-44, 2000. (C) 2000 Wiley-Liss, Inc.