Serotonergic lesions of the periaqueductal gray, a primary source of serotonin to the nucleus paragigantocellularis, facilitate sexual behavior in male rats

Abstract

While selective serotonin reuptake inhibitors (SSRIs) are widely used to treat anxiety and depression, they also produce profound disruptions of sexual function including delayed orgasm/ ejaculation. The nucleus paragigantocellularis (nPGi), a primary source of inhibition of ejaculation in male rats, contains receptors for serotonin (5-HT). The ventrolateral periaqueductal gray (vlPAG) provides serotonin to this region, thus providing an anatomical and neurochemical basis for serotonergic regulation of the nPGi. We hypothesize that 5-HT acting at the nPGi could underlie the SSRI-induced inhibition of ejaculation in rodents. To this end, we produced 5-HT lesions of the source of 5-HT to the nPGi (the vlPAG) and examined sexual behavior. Removing the source of 5-HT to the nPGi facilitated genital reflexes, but not other aspects of sexual behavior, consistent with our hypothesis. Namely, 5-HT lesions produced a significant increase in the mean number of ejaculations and a significant decrease in ejaculation latency as compared to sham lesioned animals, while latency to mating and the post-ejaculatory interval did not differ. These data suggest that the serotonergic vlPAG-nPGi pathway is an important regulatory mechanism for the inhibition of ejaculation in rats, and supports the hypothesis that this circuit contributes to SSRI-induced inhibition of ejaculation.

Wired for behaviors: from development to function of innate limbic system circuitry

“…The mPN then signals to the ventral tegmental area (VTA) and nucleus accumbens (NuAc) to initiate appetitive phase responses such as sniffing. The same circuit (VNO-AOB-MeA-BNST-mPN) also controls consummatory phase behaviors such as mounting, intromission and ejaculation via afferents to VMHvl and then areas of the midbrain and spinal cord: periaqueductal gray (PAG), nucleus paragiganta and finally the lumbosacral spinal cord (see Figure 3A ) (Marson, 2004 ; Normandin and Murphy, 2011a , b ).…”

A galanin-positive population of lumbar spinal cord neurons modulates sexual excitation and copulatory behavior

“…Important clues come from experiments in anesthetized male rats, where stimulation of the penis (via electrical stimulation of the dorsal penile nerve) was shown to elicit ejaculation in spinalized animals, but not intact ones (Marson and McKenna, 1990, Pescatori et al ., 1993). While this result suggests that genital stimulation can trigger the ejaculatory reflex per se, descending inhibitory signals to the spinal cord must modulate the impact of such incoming sensory input to prevent the inadvertent activation of the ejaculatory reflex (Coolen et al ., 2004; Carro-Juárez and Rodríguez-Manzo, 2008), contributing to a view of the brain as a “spinal-reflex inhibitor“, in addition to a central organizer of sexual behavior (Marson and McKenna, 1992, 1996; Pescatori et al ., 1993; Normandin and Murphy, 2011). However, an integral question remains unanswered - what spinal circuit does the descending input modulate?…”

Glutamatergic cells in the periaqueductal gray matter mediate sensory inputs after bladder stimulation in freely moving rats

“…There is not much known about the micturition‐related pathways involving the PAG by serotoninergic cells. However, the serotoninergic vlPAG is an important regulatory mechanism for the inhibition of ejaculation in rats, and might contribute to selective serotonin receptor inhibitor‐induced inhibition of ejaculation; although, regulation of the autonomic function of the genital organs is somewhat different from that of the bladder . The bladder's intramural ganglia, dorsal root ganglia and spinal cord contain nitric oxide, which also shows plasticity after pathological lesions, such as pelvic nerve injury, chronic bladder irritation and urethral obstruction .…”