5-HT_2A and 5-HT_2C Serotonin Receptors Differentially Modulate Mouse Sexual Arousal and the Hypothalamo-Pituitary-Testicular Response to the Presence of a Female

Abstract

The role of 5-HT_2A and 5-HT_2C subtypes of serotonergic receptors in the control of sexual behavior and plasma testosterone regulation was studied in male CBA mice exposed to a sexually receptive female separated by a transparent partition. Introduction of the receptive female induced sexual motivation and arousal in males, as evidenced by a prolonged time spent at the partition, unsuccessful attempts to step across it and a significant increase in plasma testosterone levels. Administration of 5-HT_2A receptor antagonists ketanserin (1.0 and 2.0 mg/kg i.p.) or cyproheptadine (1.0 and 2.0 mg/kg i.p.) diminished the behavioral components and prevented the hormonal components of male sexual arousal. Administration of the selective 5-HT_2C antagonist RS 102221 (1.0 and 2.0 mg/kg) considerably increased the time spent by males at the partition (p < 0.001) and, at the dose of 2.0 mg/kg, increased plasma testosterone levels (p < 0.01). Administration of ritanserin – a nonselective 5-HT_2A/2C antagonist and, to a smaller degree, 5-HT_2B antagonist – at doses of 0.1 and 0.5 mg/kg did not significantly influence male behavior and the activating effect of the presence of a female on the hypothalamo-pituitary-testicular system, although it increased resting testosterone levels (p < 0.05). The present findings suggest that 5-HT_2A/5-HT_2C receptors may be involved in the neural control of male sexual motivation and arousal, presumably by exerting reciprocal facilitative (5-HT_2A) or suppressive (5-HT_2C) influences.

Evidence of 5-HT components in human sperm: implications for protein tyrosine phosphorylation and the physiology of motility

“…As 5-HT is a molecule involved in many physiological functions (Popova & Amstislavskaya 2002, Gaspar et al 2003, Hull et al 2004, Adayev et al 2005, and because it is synthesized, degraded, and stored directly in the human sperm, we postulate that 5-HT may participate as a regulator of particular physiological processes in animal sperm. Taken together, the current findings support an important role of 5-HT on the migration of sperm throughout the female tract.…”

“…At the reproductive level, 5-HT controls libido and sexual behavior in mammals through a hormonal mechanism induced by the neurons of the preoptic area of the hypothalamus (Popova & Amstislavskaya 2002, Hull et al 2004.…”

Effects of 5-hydroxytryptamine 2C receptor agonist MK212 and 2A receptor antagonist MDL100907 on maternal behavior in postpartum female rats

“…In several motivated behaviors, 5-HT 2A and 5-HT 2C receptors also exert opposing effects. For example, Popova and Amstislavskaya reported that administration of 5-HT 2A receptor antagonist ketanserin diminished male sexual motivation and behavioral responses, whereas administration of the selective 5-HT 2C antagonist RS 102221 increased sexual motivation (Popova and Amstislavskaya, 2002). Also, impulsive action induced by amphetamine, cocaine and MK801 is reduced by 5-HT 2C receptor agonists and 5-HT 2A receptor antagonists (Fletcher et al, 2011).…”

mRNA expression profile of serotonin receptor subtypes and distribution of serotonergic terminations in marmoset brain

“…Many studies have suggested independent, reciprocal, opposing and balancing functional features associated with 5HT2A and 5HT2C receptors (Popova and Amstislavskaya, 2002; Winstanley et al, 2004; Nonogaki et al, 2006; Aloyo et al, 2009; Halberstadt et al, 2009). In the hypothalamo-pituitary-testicular -based system, the neural control of male sexual motivation and arousal involves the facilitative action of 5HT2A and suppressive action of 5HT2C in a reciprocal manner (Popova and Amstislavskaya, 2002).…”