Corticosterone rapidly modulates dorsomedial hypothalamus serotonin and behavior in an estrogen- and progesterone-dependent manner in adult female rats: potential role of organic cation transporter 3 (OCT3).

Previous studies have shown that corticosterone rapidly alters extracellular serotonin (5-hydroxytryptamine; 5-HT) concentrations in the dorsomedial hypothalamus (DMH) of adult male rats, suggesting a role for corticosterone actions in the DMH in regulation of physiological and behavioral responses. Whether or not corticosterone also rapidly alters extracellular serotonin concentrations in the DMH of female rats, and the dependence of this effect on ovarian hormones, is not known. To determine the effects of 17β-estradiol (E2), progesterone (P), and corticosterone on extracellular concentrations of serotonin in the DMH, corticosterone and/or P were delivered into the DMH of ovariectomized rats via reverse microdialysis in E2-primed rats. Combined, but not separate, delivery of corticosterone and P into the DMH rapidly and transiently increased extracellular 5-HT concentrations, a result that was dependent upon circulating E2. This effect of corticosterone on DMH 5-HT was replicated by local perfusion of the organic cation transporter 3 (OCT3) competitive inhibitor normetanephrine. Intra-DMH infusions of either corticosterone or normetanephrine also reversibly suppressed lordosis responses in E2 + P-primed females. These results suggest that ovarian hormones in combination with corticosterone modulate OCT3-mediated 5-HT clearance in the DMH, potentially representing an adaptive mechanism that allows sexually receptive females to respond rapidly to acute stressors.