Serotonin 5-HT<sub>1A</sub> Receptor mRNA Expression in Dorsal Hippocampus and Raphe Nuclei after Gonadal Hormone Manipulation in Female Rats

Abstract

Female ovarian steroids influence mood and cognition, an effect presumably mediated by the serotonergic system. A key receptor in this interplay may be the 5-HT(1A) receptor subtype. We gave adult ovariectomized female rats subcutaneous pellets containing different dosages of 17 beta-estradiol alone or in combination with progesterone, or placebo pellets, for 2 weeks. 5-HT(1A) receptor mRNA levels were analyzed by in situ hybridization in the dorsal hippocampus, dorsal and median raphe nuclei, and entorhinal cortex. Estradiol treatment alone reduced 5-HT(1A) gene expression in the dentate gyrus and the CA2 region (17 and 19% decrease, respectively). Estradiol combined with progesterone supplementation increased 5-HT(1A) gene expression versus placebo in the CA1 and CA2 subregions of the dorsal hippocampus (16 and 30% increase, respectively). Concomitantly, 5-HT(1A) mRNA expression was decreased by 13% in the ventrolateral part of the dorsal raphe nuclei, while no changes were found in the median raphe nucleus and entorhinal cortex. Chronic effects of ovarian hormones on 5-HT(1A) receptor mRNA expression appear tissue-specific and involve hippocampal subregions and the raphe nuclei. Modulation of 5-HT(1A) receptor gene expression may be of importance for gonadal steroid effects on mood and cognition.