Serotonin 5-HT_1A 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 17β-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.

Estrogen and Progesterone Prevent Disruption of Prepulse Inhibition by the Serotonin-1A Receptor Agonist 8-Hydroxy-2-dipropylaminotetralin

“…In addition, estrogen induces progesterone receptor expression in the dorsal raphe nucleus (Bethea, 1994). Previous studies have suggested that estrogen reduces 5-HT 1A receptor gene expression and the addition of progesterone enhances this effect on 5-HT 1A autoreceptors (Pecins- Thompson and Bethea, 1999) but reverses the effect of estrogen on the postsynaptic 5-HT 1A receptors (Birzniece et al, 2001). Therefore, one explanation for the present results could be that estrogen induces progesterone receptor expression in the dorsal raphe nucleus, and together these hormones significantly inhibit 5-HT 1A autoreceptor expression, reducing the effect of 8-OH-DPAT on PPI.…”

“…Estrogen has been found to reduce 5-HT 1A receptor gene expression in the dorsal raphe nucleus (Pecins- Thompson and Bethea, 1999), regions of the hippocampus (Birzniece et al, 2001) and amygdala (Ö sterlund and Hurd, 1998). Progesterone further reduces 5-HT 1A receptor gene expression in the dorsal raphe nucleus of estrogen-primed animals (Pecins- Thompson and Bethea, 1999); however, it increases 5-HT 1A receptor gene expression in the hippocampus (Birzniece et al, 2001).…”

“…Progesterone further reduces 5-HT 1A receptor gene expression in the dorsal raphe nucleus of estrogen-primed animals (Pecins- Thompson and Bethea, 1999); however, it increases 5-HT 1A receptor gene expression in the hippocampus (Birzniece et al, 2001). Therefore, in the present study, we focus on the interaction of estrogen and progesterone with 5-HT 1A receptors.…”

A Postpartum Model in Rat: Behavioral and Gene Expression Changes Induced by Ovarian Steroid Deprivation

“…Rats underwent ovariectomy (OVX) followed by continuous release pellet implantation (.5 mg of 17β estradiol [E2] and 50 mg of progesterone [P4] 21-day release or placebo) (Innovative Research of America, Sarasota, Florida) under pentobarbital/ atropine anesthesia to mimic serum levels of those during human pregnancy (11). After 21 days treatment, the hormone pellets were completely removed under isoflurane anesthesia.…”

“…However, this regimen was based on the plasma concentration of estrogen and progesterone that occurs in the course of rat pregnancy, where progesterone peaks during the middle of gestation and falls to estrous cycle levels by the time of delivery (10). Conversely in humans, both estrogen and progesterone increase gradually throughout the pregnancy (11). Progesterone has been shown to alter neurotransmission, indicating a crucial role in the pathophysiology of PPD (3).…”