Fluoxetine-induced decrements in sexual responses of female rats and hamsters are reversed by 3α,5α-THP.
BACKGROUND
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.


OBJECTIVE
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.


METHODS
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.
Frye
Cheryl A
CA
Departments of Psychology and Biology, Centers for Neuroscience and Life Sciences Research, University at Albany, SUNY, Albany, NY, USA. cafrye@albany.edu
Rhodes
Madeline E
ME
D000374:Aggression / Q000187:drug effects; D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000633:toxicity*; D001931:Brain Mapping; D006224:Cricetinae; D005260:Female; D005473:Fluoxetine / Q000633:toxicity*; D007267:Injections; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D011280:Pregnanolone / Q000494:pharmacology*; D051381:Rats; D012726:Sexual Behavior, Animal / Q000187:drug effects*; D017557:Ventral Tegmental Area / Q000187:drug effects*
D018687:Antidepressive Agents, Second-Generation; D005473:Fluoxetine; D011280:Pregnanolone
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