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


OBJECTIVE
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.


METHODS
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.
Snoeren
Eelke
E
Department of Psychopharmacology, Utrecht Institute for Pharmaceutical Sciences and Rudolf Magnus Institute of Neuroscience, Utrecht University, Utrecht, The Netherlands. e.m.s.snoeren@uu.nl
Chan
Johnny
J
Bovens
Astrid
A
Cuppen
Edwin
E
Waldinger
Marcel
M
Olivier
Berend
B
Oosting
Ronald
R
D000704:Analysis of Variance; D000818:Animals; D005260:Female; D055786:Gene Knockout Techniques; D051381:Rats; D017208:Rats, Wistar; D044282:Receptor, Serotonin, 5-HT1A / Q000187:drug effects / Q000235:genetics*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics*; D012726:Sexual Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D013223:Statistics as Topic; D018709:Statistics, Nonparametric
D050486:Serotonin Plasma Membrane Transport Proteins; D044282:Receptor, Serotonin, 5-HT1A