Effects of nitric oxide stimulation on the brain

Nitric oxide (NO) is known as the neurotransmitter responsible for penile erection. Recent experimental studies showed that NO is recognized as an important messenger mediating male copulatory behavior and penile erection in the central nervous system. In this article, the roles of central NO on modulation of male copulatory behavior and penile erection in male rats are reviewed mainly based on our previous experimental results. We focused on two brain areas in the hypothalamus for this purpose: the medial preoptic area (MPOA) and paraventricular nucleus (PVN). Increase in extracellular NO level in the MPOA facilitates copulatory behaviors, while decreases in the NO level reduce them. The altered NO level in the PVN increases frequency of reflexive erections, but does not affect copulatory behavior. Taken together, the current results and previous reports suggest that central NO may modulate male sexual functions and NO in two distinct brain areas and may play different roles through activation of different neurotransmitters. Activities of NO in the hypothalamus are affected by the existence of gonadal steroids. Moreover, our experimental results clearly showed that the extracellular NO level in the MPOA and PVN decreased with aging, and testosterone replacement in aged rats restored NO levels in both brain areas. These results postulate that changes of central NO with aging and following hormone replacement might partly contribute to changes in male rats sexual behavior corresponding to aging and replacement. Moreover, our recent report demonstrated that long-term testosterone replacement in aged rats is more effective for restoration of sexual behavior, which may be partly induced by central NO, than high-dose, short-term replacement.