Excitotoxic lesions of the nucleus paragigantocellularis facilitate male sexual behavior but attenuate female sexual behavior in rats

Abstract

Little is known regarding the descending inhibitory control of genital reflexes such as ejaculation and vaginal contractions. The brainstem nucleus paragigantocellularis (nPGi) projects bilaterally to the lumbosacral motoneuron pools that innervate the genital musculature of both male and female rats. Electrolytic nPGi lesions facilitate ejaculation in males, leading to the hypothesis that the nPGi is the source of descending inhibition to genital reflexes. However, the function of the nPGi in female sexual behavior remains to be elucidated. To this end, male and female rats received bilateral excitotoxic fiber-sparing lesions of the nPGi, and sexual behavior and sexual behavior-induced Fos expression were examined. In males, nPGi lesions facilitated copulation, supporting the hypothesis that the nPGi, and not fibers-of-passage, is the source of descending inhibition of genital reflexes in male rats. nPGi lesions in males did not alter sexual behaviorinduced Fos expression in any brain region examined. nPGi-lesioned females spent significantly less time mating with stimulus males and had significantly longer ejaculation-return latencies compared to baseline. These results did not significantly differ from control females, but this trend warranted further analysis of the reinforcing value of sexual behavior. Both lesioned and nonlesioned females formed a conditioned place preference (CPP) for artificial vaginocervical stimulation (aVCS). However, post-reinforcement, nPGi-lesioned females did not differ in the percentage of time in spent in the non-reinforced chamber versus the reinforced chamber, suggesting a weakened CPP for aVCS. nPGi lesions in females reduced sexual behavior-induced Fos expression throughout the hypothalamus and amygdala. Taken together, these results suggest that while nPGi lesions in males facilitate copulation, such lesions in females attenuate several aspects of sexual behavior resulting in a reduction in the rewarding value of copulation that may be mediated by nPGi control of genital reflexes. This work has important implications for the understanding and treatment of sexual dysfunction in people including delayed/premature ejaculation, involuntary vaginal spasms, and pain during intercourse.Correspondence to: Anne Z. Murphy, Ph.D., Neuroscience Institute, Georgia State University, PO Box 5030, Atlanta, amurphy@gsu.edu, Phone: 404.413.5332, Fax: 404.413.5301. 1 Present address: Netherlands Institute for Neuroscience, Neuroendocrinology Group, Meibergdreef 47, 1105 BA, Amsterdam, The Netherlands, j.normandin@nin.knaw.nl Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that a...

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

“…To induce sexual receptivity, ovariectomized female rats were injected with β-estradiol-3-benzoate (10ug/0.1ml sesame oil s.c.; Sigma Aldrich) 48 hours before testing and progesterone (500ug/0.1ml sesame oil s.c.; Fluka) 4 hours before testing as previously described (Barfield and Lisk, 1970; McEwen et al, 1987; Normandin and Murphy, 2010; Quadagno et al, 1972). …”

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“…While both nPGi lesioned and non-lesioned females formed a conditioned place preference for aCVS, the amount of time lesioned females spent in the non-reinforced chamber versus the reinforced chamber did not differ, indicating a weakened CPP for aVCS. These data suggest that nPGi lesions produce dysregulation of genital function that feeds back on reward systems (Normandin and Murphy, 2011). Further testing of the effect of nPGi lesions on the physiology of the pelvic muscles in females is needed to confirm this hypothesis.…”

“…Electrolytic (Yells et al, 1992; Yells et al, 1994) or neurotoxic (Normandin and Murphy, 2011) lesions of the nPGi in male rats consistently result in the facilitation of sexual behavior, as indicated by a decrease in mount and intromission frequency, ejaculation latency, and an increase the number of ejaculations to satiety. nPGi lesions also decrease the latency to- and increase the number of ex copula erections (Marson et al, 1992; Marson and McKenna, 1990).…”

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