Estrogen selectively increases tryptophan hydroxylase-2 mRNA expression in distinct subregions of rat midbrain raphe nucleus: association between gene expression and anxiety behavior in the open field.
BACKGROUND
Ovarian steroids modulate anxiety behavior, perhaps by regulating the serotonergic neurons in the midbrain raphe nucleus. The regulation of the brain-specific isoform of rat tryptophan hydroxylase (TPH2) by ovarian hormones has not yet been investigated. Therefore, we examined the effects of estrogen and progesterone on TPH2 mRNA in the rat dorsal and median raphe nuclei (DRN and MRN, respectively) and whether TPH2 mRNA levels correlated with anxiety behavior.


METHODS
Ovariectomized rats were treated for two weeks with placebo, estrogen or estrogen plus progesterone, exposed to the open field test, and TPH2 mRNA was quantified by in situ hybridization histochemistry.


RESULTS
Estrogen increased TPH2 mRNA in the mid-ventromedial and caudal subregions of the DRN and the caudal MRN. Combined estrogen and progesterone treatment did not change TPH2 mRNA relative to ovariectomized controls. TPH2 mRNA in caudal DRN was associated with lower anxiety-like behavior, whereas TPH2 mRNA in rostral dorsomedial DRN was associated with increased anxiety-like behavior.


CONCLUSIONS
These results suggest that estrogen may increase the capacity for serotonin synthesis in discrete subgroups of raphe neurons, and reinforce previous observations that different subregions of DRN contribute to distinct components of anxiety behavior.
Hiroi
Ryoko
R
Department of Psychology, University of Washington, Seattle, Washington 98195, USA.
McDevitt
Ross A
RA
Neumaier
John F
JF
D000818:Animals; D001007:Anxiety / Q000235:genetics* / Q000378:metabolism; D001522:Behavior, Animal; D003720:Densitometry / Q000379:methods; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression / Q000235:genetics / Q000502:physiology*; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D010052:Ovariectomy; D011374:Progesterone / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D011903:Raphe Nuclei / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013037:Spatial Behavior; D014365:Tryptophan Hydroxylase / Q000096:biosynthesis* / Q000235:genetics
D004967:Estrogens; D012333:RNA, Messenger; D011374:Progesterone; D014365:Tryptophan Hydroxylase; C504569:tph2 protein, rat