A New Female Rat Animal Model for Hypoactive Sexual Desire Disorder; Behavioral and Pharmacological Evidence

Abstract

Introduction Female sexual dysfunction (FSD) affects 33–48% of women. Female rats with low sexual activity might model FSD. Aim In this study, we have investigated whether in a population of normal female rats, subpopulations of rats exist with different levels of sexual behavior. Methods Sexually experienced, intact, estradiol-primed female rats were placed in an empty compartment adjacent to a compartment with a male. The females were allowed, during 30 minutes, to switch between the compartments via a hole through which only the females could pass (paced mating). Next, we investigated the acute effects on female sexual behavior of apomorphine, a D1- and D2-type dopamine receptor agonist, (+/–)-8-hydroxy-2-(dipropylamino)tetralin hydrobromide (±8-OH-DPAT), a 5-HT1A receptor agonist, and paroxetine, a selective serotonin reuptake inhibitor. Main Outcome Measures Time spent in compartments, proceptive behaviors, contact–return latencies, and percentages of exits were quantified. Results Based on their behavior in the paced mating sex test, estradiol-primed, intact female rats can be divided into three groups: those that mostly avoid the male, a large middle group, and those that mostly approach the male. The avoiders also showed significantly less proceptive behavior than the male approachers. The sexual behavior of the females was relatively stable over time, suggesting the existence of different endophenotypes in female rats. Apomorphine and ±8-OH-DPAT had an inhibiting effect on sexual behavior, but only females dosed with apomorphine showed a different response in avoiders and approachers, more inhibiting effect in avoiders than approachers. Paroxetine had no effect on proceptive behavior. Discussion The stable, male-avoiding behavior of some females might correspond to the characteristics of women with FSD. Therefore, these avoiders are a promising new model for FSD, specifically for sexual desire and/or arousal disorders. Furthermore, the apomorphine data suggest that differences in the dopamine system may (partly) underlie the differences in sexual behaviors between avoiders and approachers.

Pharmacology of serotonin and female sexual behavior

“…Consistent with this is a recent report that systemic treatment with 8-OH-DPAT reduced proceptivity and also reduced the time females spent in the male’s compartment in a pacing paradigm (Snoeren et al, 2010; Snoeren et al, 2011a; Snoeren et al, 2011b). Because both effects were attenuated by the 5-HT 1A receptor antagonist, WAY100635 (Snoeren et al, 2010; Snoeren et al, 2011b), a 5-HT 1A receptor-mediated effect was implicated.…”

Factors associated with sexual arousal, sexual sensation seeking and sexual satisfaction among female African American adolescents

“…Genotyping results were used to form two groups of participants: those homozygous for the long allele (0) and those with either 1 or 2 copies of the short allele (1). Based on prior findings indicating an association between 5-HTTLPR and behavioral inhibition tendencies in general (57), we hypothesize that possessing at least one copy of the short (S) allele will be inhibitory for sexuality-related factors (25, 26, 34). For DRD4, DRD4 genotypes were grouped as 7R- (both alleles less than 7-repeats) (0) or 7R+ (at least one allele 7-repeats or longer) (1); the 7R+ genotype was present in 46.5% of the sample.…”

“…While often omitted in public health research, biological influences on sexual behaviors, such as the neurohormones dopamine and serotonin, appear to play an important role in sexual experience and have been well described in sexual behaviors of rodents, particularly male rodents (22-26). When neurons containing dopamine or serotonin are stimulated, they release their respective neurohormone into the synpatic cleft where it is able to travel and bind to receptors on the postsynaptic neuron.…”

“…In animal and human literature, the release of dopamine has been associated with motivation and reward related behaviors (27) and higher levels of dopamine increase sexual motivation and engagement in sexual behaviors among male rodents (23, 24, 28). In contrast, the release of serotonin has an inhibitory influence on sexual behaviors, and increased serotonin levels leads to decreased engagement in sexual behaviors among males (22-26). The role of dopamine and serotonin in female sexual behavior is less understood.…”

“…Therefore, those with the s-allele have reduced rates of serotonin clearance and increased serotonin presence in the synaptic cleft. In animals, male rodents with the functional equivalent of the s-allele were found to have reduced initation and engagement in sexual behaviors (25), though findings were less conclusive for females (47). In humans, blockade of the serotonin transporter by selective serotonin reuptake inhibitors (SSRIs), a commonly used treatment for depression, result in increased serotonin presence in the synaptic cleft.…”