Sexual responses of female rats and hamsters are reversed by 3α,5α-THP

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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 & #945;-pregnan-3 & #945;-ol-20-one (3 & #945;,5

& #945;-THP). 3 & #945;,5 & #945;-THP plays a key role in female reproductive

physiology and behavior.

AIMS:

This study aimed to determine whether 3 & #945;,5 & #945;-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

& #945;,5 & #945;-THP, then fluoxetine will inhibit sexual receptivity concomitant

with reducing 3 & #945;,5 & #945;-THP levels, effects which can be reversed by 3

& #945;,5 & #945;-THP administration.

METHODS:

& #8194; Experiment 1 investigated effects of acute systemic fluoxetine [20 mg/kg

intraperitoneal (IP)] and/or 3 & #945;,5 & #945;-THP [500 µg, subcutaneous (SC)]

administration on sexual responding of ovariectomized, hormone-primed rats.

Experiment 2 examined effects of 3 & #945;,5 & #945;-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 & #945;,5

& #945;-THP. Intra-VTA 3 & #945;,5 & #945;-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.

http://www.ncbi.nlm.nih.gov/pubmed/20412429