Progesterone's modulation of serotonin 1A receptor functioning in the ovariectomized estrogen-treated rat

The focus of this study was to determine if progesterone regulates serotonergic control of lordosis behavior in estradiol benzoate (EB)-primed ovariectomized (OVX) rats. It was predicted that progesterone would decrease the lordosis-inhibiting effects of the 5-HT1A receptor agonist, 8-0H-DPAT. The drug, given systemically, was indeed less effective at inhibiting the lordosis reflex in the EP (rats primed with 10 J.tg EB and 500 J.tg progesterone 48 hr later) rats when compared to the EO (rats primed with 10 J.tg EB and oil 48 hr later) rats. Furthermore, when the OVX rats were preprimed with EB (10 J.tg EB, 7 days prior to hormone priming), a greater attenuation of the lordosisinhibiting effect of 8-0H-DPAT was present in the EP preprimed rats compared to the EO preprimed rats. It was hypothesized that the reduction in potency of 8-0H-DPAT to inhibit lordosis behavior after progesterone priming was related to one of these three mechanisms: (1) decreasing extracellular 5-HT, (2) decreasing the effectiveness of 5-HT1A receptors in the ventromedial nucleus of the hypothalamus (VMN) or (3) increasing the ability of 5-HT2A1zc receptors to enhance lordosis behavior, masking the effects of the 5-HT IA receptor agonists. Microdialysis of OVX rats was used to determine that progesterone (500 J.tg) after EB (2.5 or 25 J.tg) reduced extracellular 5-HT. 5-HT levels were reduced to the limits of detectability in the medial basal hypothalamus (MBH), while rats given either dose of EB without progesterone had extracellular 5-HT levels similar to vehicle treatment. When 8-0H-DPAT was infused directly into the VMN, there was no difference in lordosis behavior of EP or EO rats, and no apparent effects of progesterone to decrease the effectiveness of 5-HT1A receptors in the VMN were observed. Lastly, the effects of progesterone on the 5-HT2AI2c receptor-mediated behaviors, wet dog shakes and back muscle contractions, were examined. Progesterone priming in EB-primed OVX rats produced no differences in either behavior compared to EB-primed OVX rats. It is likely that the progesteroneinduced decrease in potency of 8-0H-DPAT to inhibit lordosis behavior is related to decreased endogenous levels of extracellular 5-HT.