Estrogen decreases 5-HT1B autoreceptor mRNA in selective subregion of rat dorsal raphe nucleus: inverse association between gene expression and anxiety behavior in the open field.
We have recently shown that estrogen decreases anxiety and increases expression of tryptophan hydroxylase-2 (TPH2), the rate-limiting enzyme for 5-HT synthesis. However, the effects of estrogen on 5-HT release and reuptake may also affect the overall availability of 5-HT in the forebrain. Estrogen has been previously shown to have no effect on the inhibitory 5-HT 1A autoreceptor (5-HT(1A)) in the rat dorsal raphe nuclei (DRN); however the regulation of the inhibitory 5-HT 1B autoreceptor (5-HT(1B)) in the midbrain raphe by estrogen has not yet been investigated. Therefore, we examined the effects of estrogen on 5-HT(1B) mRNA in the rat DRN, focusing on specific subregions, and whether 5-HT(1B) mRNA levels correlated with TPH2 mRNA levels and with anxiety-like behavior. Ovariectomized rats were treated for 2 weeks with estrogen or placebo, exposed to the open field test, and 5-HT(1A) and 5-HT(1B) mRNA was quantified by in situ hybridization histochemistry. Estrogen had no effect on 5HT(1A) mRNA in any of the DRN subregions examined, confirming a previous report. In contrast, estrogen selectively decreased 5-HT(1B) mRNA in the mid-ventromedial subregion of the DRN, where 5-HT(1B) mRNA was associated with higher anxiety-like behavior and inversely correlated with TPH2 mRNA levels. These results suggest that estrogen may reduce 5-HT(1B) autoreceptor and increase TPH2 synthesis in a coordinated fashion, thereby increasing the capacity for 5-HT synthesis and release in distinct forebrain regions that modulate specific components of anxiety behavior.
Hiroi
R
R
Department of Psychology, University of Washington, Seattle, WA 98195, USA.
Neumaier
J F
JF
D000818:Animals; D015536:Down-Regulation / Q000187:drug effects*; D004967:Estrogens / Q000494:pharmacology*; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology*; D005260:Female; D010052:Ovariectomy / Q000379:methods; D012333:RNA, Messenger / Q000378:metabolism*; D011903:Raphe Nuclei / Q000033:anatomy & histology / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044282:Receptor, Serotonin, 5-HT1A / Q000235:genetics / Q000378:metabolism; D044302:Receptor, Serotonin, 5-HT1B / Q000235:genetics* / Q000378:metabolism; D013223:Statistics as Topic; D014365:Tryptophan Hydroxylase / Q000235:genetics / Q000378:metabolism
D004967:Estrogens; D012333:RNA, Messenger; D044302:Receptor, Serotonin, 5-HT1B; D044282:Receptor, Serotonin, 5-HT1A; D014365:Tryptophan Hydroxylase; C504569:tph2 protein, rat