Chronic paroxetine treatment does not affect sexual behavior in hormonally sub-primed female rats despite 5-HT₁(A) receptor desensitization.
BACKGROUND
Selective serotonin reuptake inhibitors (SSRIs) cause sexual dysfunctions in humans. However, because SSRIs are used to treat depression, it is unclear whether the problems are caused by the drug, by the depression itself, or an interaction between both.


OBJECTIVE
The present study investigated the effects of chronic paroxetine treatment on sexual behavior in female rats. Furthermore, we tested whether 5-hydroxytryptamine (5-HT)₁(A) receptors were desensitized in these females.


METHODS
Ovariectomized female rats, either sub-primed with estradiol or fully primed with estradiol and progesterone, were tested in a paced mating test. Proceptive (darting and hopping), receptive (lordosis), and paced mating-related (percentages of exits and contact-return latencies) behaviors were quantified during the course of 56 days of chronic paroxetine treatment (10 mg/kg and 20 mg/kg per day). The 5-HT₁(A) /5-HT₇ receptor agonist (±)-8-hydroxy-2-(dipropylamino)tetralin hydrobromide ((±)8-OH-DPAT) alone and in combination with the selective 5-HT₁(A) receptor antagonist WAY-100635 was administered to study putative 5-HT₁(A) desensitization in the same females.


METHODS
Proceptive, receptive, and paced mating behaviors were quantified.


RESULTS
Acute and chronic paroxetine treatment did not change proceptive and receptive behaviors in both sub-primed and fully primed female rats. In all groups, (±)8-OH-DPAT showed a clear dose-dependent inhibition of sexual behaviors in vehicle-treated females and a right-shifted dose-response effect in the paroxetine-treated rats. WAY-100635 attenuated the inhibiting effect of the 5-HT₁(A) receptor agonist in all females. These data suggest 5-HT₁(A) receptor desensitization after chronic paroxetine treatment.


CONCLUSIONS
Chronic paroxetine treatment does not cause sexual side effects in sub- or fully hormonally primed female rats. Furthermore, chronic treatment causes adaptive changes in the serotonin system such as desensitization of 5-HT₁(A) receptors, which may counteract the inhibiting effects of increased extracellular serotonin levels in the chronic paroxetine-treated rats.
Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences and Rudolf Magnus Institute of Neuroscience, Utrecht University, Utrecht, The Netherlands.
Eelke M S
EM
Snoeren
Louise K
LK
Refsgaard
Marcel D
MD
Waldinger
Berend
B
Olivier
Ronald S
RS
Oosting
D000704:Analysis of Variance; D000818:Animals; D000928:Antidepressive Agents / Q000009:adverse effects / Q000494:pharmacology*; D003888:Desensitization, Immunologic; D004958:Estradiol; D005260:Female; D008297:Male; D010052:Ovariectomy; D017374:Paroxetine / Q000009:adverse effects / Q000494:pharmacology*; D011374:Progesterone; D051381:Rats; D017208:Rats, Wistar; D044282:Receptor, Serotonin, 5-HT1A / Q000187:drug effects*; D012726:Sexual Behavior, Animal / Q000187:drug effects*; D013997:Time Factors
D000928:Antidepressive Agents; D044282:Receptor, Serotonin, 5-HT1A; D017374:Paroxetine; D011374:Progesterone; D004958:Estradiol