Anatomy and Physiology of the Nucleus Paragigantocellularis: Neural Regulation of Genital Reflexes in Male and Female Rats

The supraspinal control of descending inhibition of genital reflexes (such as ejaculation) is poorly understood but is important in our global comprehension of how neural signals are integrated to produce sexual behavior, and in our understanding of sexual dysfunction. Sexual dysfunctions, such as premature ejaculation/delayed ejaculation in men, and involuntary vaginal spasms, dyspareunia, and anorgasmia in women, are common. An underlying dysregulation of genital reflexes may produce these dysfunctions, especially in those individuals being treated for depression and anxiety with serotonergic drugs. The nucleus paragigantocellularis (nPGi) of the rat medulla has been described as a descending inhibitory system for genital reflexes in rats, and a homologue is known in humans. Through retrograde tracing of nPGi afferents with the tracer Fluorogold in rats, we found that a number of brain regions implicated in sexual behavior, such as the medial preoptic area, paraventricular nucleus of the hypothalamus, and periaqueductal gray (PAG) provide sexually dimorphic projections to the nPGi, and that many of these regions contain receptors for gonadal steroids and are active during sexual behavior. We also found that excitotoxic lesions of the nPGi with N-methyl-D-aspartate facilitate male sexual behavior by reducing the number of intromissions required for ejaculation, and decreasing ejaculation latency. In females, such lesions attenuated sexual behavior by reducing the amount of time the female spent mating and reducing the reinforcement value of vaginocervical stimulation. Lastly, we found that by removing the source of serotonin to the nPGi (from the ventrolateral PAG) with the serotonergic neurotoxin 5,7-DHT in male rats, we were able to mimic the effects of nPGi lesions and facilitated male sexual behavior indicating that serotonin neurotransmission at the level of the nPGi is critical for genital reflex control. Taken together our results indicate that the nPGi is an important site of integration of internal signals for the regulation of sexual behavior that is sexually dimorphic and under serotonergic control. Our understanding of normal and dysfunction genital reflex control, and possible treatment options in people, is complemented by these results. INDEX WORDS: Sex differences, Fos, Estrogen, Androgen, Brainstem, Penis, Vagina, Orgasm ANATOMY AND PHYSIOLOGY OF THE NUCLEUS PARAGIGANTOCELLULARIS: NEURAL REGULATION OF GENITAL REFLEXES IN MALE AND FEMALE RATS