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Serotonin transporter null mutation and sexual behavior in female rats: 5-HT1A receptor desensitization

Snoeren, E. and Chan, J.Y. and Bovens, A. and Cuppen, E. and Waldinger, M. and Olivier, B. and Oosting, R. (2010) Serotonin transporter null mutation and sexual behavior in female rats: 5-HT1A receptor desensitization. Journal of Sexual Medicine, 7, 2424-34. ISSN 1743-6095.

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INTRODUCTION: Serotonin plays a key role in sexual behavior. In serotonin transporter (SERT) knockout rats (-/-), basal extracellular 5-HT levels are considerably increased, indicating a serotonergic disturbance. Heterozygous SERT(+/-) rats express 50% of SERT in comparison to wild-type rats and may therefore model the s/s phenotype of the human SERT promoter (5-HTTLPR) polymorphism. AIM: In the present study, we used both homozygote and heterozygote SERT knockout and wild-type rats (+/+) to study the putative role of the SERT in female sexual behavior. METHODS: Female rats were brought into estrous by hormonal injections before a paced mating sex test. The effects of the 5-HT(1A)/5-HT(7) receptor agonist (+/-)-8-hydroxy-2-(dipropylamino)tetralin hydrobromide (+/-8-OH-DPAT) (0.03-1 mg/kg s.c.) and the 5-HT(1A) receptor antagonist WAY-100635 (0.1-1-mg/kg i.p.) on sexual behaviors of the females were tested separately and in a selected combination of both in all three genotypes. MAIN OUTCOME MEASURES: Proceptive (darting and hopping) and receptive (lordosis) behaviors were quantified. RESULTS: Basal proceptive and receptive sexual activities were not different between SERT+/+, +/- and -/- female rats. The dose-effect curve after +/-8-OH-DPAT for these activities was clearly shifted to the right in SERT-/- animals compared to other genotypes. WAY-100635 alone had no effect on sexual behavior in any genotype, but was able to antagonize the +/-8-OH-DPAT-induced decrease in sexual activities indicating the involvement of the 5-HT(1A) receptor. CONCLUSIONS: The absence (-/-) or reduced (+/-) expression of SERT does not affect basal sexual activity in female rats in a paced mating situation. The data indicate a desensitized 5-HT1A receptor in the SERT-/-, but not in the SERT+/- females. Under normal basal conditions, desensitized 5-HT1A receptors apparently do not play a role in female sexual behavior of the SERT-/-. However, upon activation of the 5-HT1A receptor in "normal" females (SERT+/+ and SERT+/-), a hyposexual behavior is induced.

Item Type:Article
Institutes:Hubrecht Instituut
ID Code:9536
Deposited On:11 Feb 2011 01:00
Last Modified:07 Sep 2011 17:01

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