Cheryl A Frye1, Madeline E Rhodes. 1. Departments of Psychology and Biology, Centers for Neuroscience and Life Sciences Research, University at Albany, SUNY, Albany, NY, USA. cafrye@albany.edu
Abstract
INTRODUCTION: Sexual dysfunction, as a result of selective-serotonin reuptake inhibitor (SSRI) treatment among women, is relatively common and is a factor in medication compliance. The mechanisms that underlie these side-effects of SSRIs are not well-understood. SSRIs can alter activity of catabolic enzymes that are involved in progesterone's conversion to 5 α-pregnan-3 α-ol-20-one (3 α,5 α-THP). 3 α,5 α-THP plays a key role in female reproductive physiology and behavior. AIMS: This study aimed to determine whether 3 α,5 α-THP, in the midbrain ventral tegmental area (VTA) may be a potential mechanism for fluoxetine's reduction in sexual responding of female rodents. We hypothesized that if fluoxetine induces decrements in sexual responding in part through actions of 3 α,5 α-THP, then fluoxetine will inhibit sexual receptivity concomitant with reducing 3 α,5 α-THP levels, effects which can be reversed by 3 α,5 α-THP administration. METHODS: Experiment 1 investigated effects of acute systemic fluoxetine [20 mg/kg intraperitoneal (IP)] and/or 3 α,5 α-THP [500 µg, subcutaneous (SC)] administration on sexual responding of ovariectomized, hormone-primed rats. Experiment 2 examined effects of 3 α,5 α-THP administration to the midbrain VTA (100 ng) on fluoxetine-induced decrements in lordosis of ovariectomized, hormone-primed rats and hamsters. MAIN OUTCOME MEASURES: Sexual responding was determined in rats and hamsters. For rats, the percentage of times that the lordosis response occurred following mounting by a sexually-vigorous male (lordosis quotients) was utilized. For hamsters, lateral displacement, the pelvic movement that females will make to facilitate intromissions by a male hamster, was utilized. RESULTS: Fluoxetine significantly reduced lordosis, and this was reversed SC 3 α,5 α-THP. Intra-VTA 3 α,5 α-THP attenuated fluoxetine's detrimental effects on lordosis quotients and lateral displacement of rats and hamsters, respectively. CONCLUSIONS: Thus, fluoxetine's effects to disrupt female sexual responses may involve its effects on progestogens in the midbrain VTA.
INTRODUCTION:Sexual dysfunction, as a result of selective-serotonin reuptake inhibitor (SSRI) treatment among women, is relatively common and is a factor in medication compliance. The mechanisms that underlie these side-effects of SSRIs are not well-understood. SSRIs can alter activity of catabolic enzymes that are involved in progesterone's conversion to 5 α-pregnan-3 α-ol-20-one (3 α,5 α-THP). 3 α,5 α-THP plays a key role in female reproductive physiology and behavior. AIMS: This study aimed to determine whether 3 α,5 α-THP, in the midbrain ventral tegmental area (VTA) may be a potential mechanism for fluoxetine's reduction in sexual responding of female rodents. We hypothesized that if fluoxetine induces decrements in sexual responding in part through actions of 3 α,5 α-THP, then fluoxetine will inhibit sexual receptivity concomitant with reducing 3 α,5 α-THP levels, effects which can be reversed by 3 α,5 α-THP administration. METHODS: Experiment 1 investigated effects of acute systemic fluoxetine [20 mg/kg intraperitoneal (IP)] and/or 3 α,5 α-THP [500 µg, subcutaneous (SC)] administration on sexual responding of ovariectomized, hormone-primed rats. Experiment 2 examined effects of 3 α,5 α-THP administration to the midbrain VTA (100 ng) on fluoxetine-induced decrements in lordosis of ovariectomized, hormone-primed rats and hamsters. MAIN OUTCOME MEASURES: Sexual responding was determined in rats and hamsters. For rats, the percentage of times that the lordosis response occurred following mounting by a sexually-vigorous male (lordosis quotients) was utilized. For hamsters, lateral displacement, the pelvic movement that females will make to facilitate intromissions by a male hamster, was utilized. RESULTS:Fluoxetine significantly reduced lordosis, and this was reversed SC 3 α,5 α-THP. Intra-VTA 3 α,5 α-THP attenuated fluoxetine's detrimental effects on lordosis quotients and lateral displacement of rats and hamsters, respectively. CONCLUSIONS: Thus, fluoxetine's effects to disrupt female sexual responses may involve its effects on progestogens in the midbrain VTA.
Authors: Sandra R Leiblum; Patricia E Koochaki; Cynthia A Rodenberg; Ian P Barton; Raymond C Rosen Journal: Menopause Date: 2006 Jan-Feb Impact factor: 2.953