Which brain areas are important for male sexual behavior?
Numerous brain areas contribute to male sexual behavior. The nigrostriatal dopamine system facilitates motor activation. The mesolimbic dopamine system contributes general activation and arousal. The medial preoptic area (MPOA) is probably the single most important integrative area for male sexual behavior.
The A 14 dopamine system supplies the MPOA with dopamine.
What is testosterone's role in male sexual behavior?
Testosterone has primarily slow, genomically mediated effects on protein synthesis. However, sexual behavior is very interactive and fast, especially in rats. (Each vaginal intromission lasts about half a second!) A major way that long-term steroid effects are translated into rapid behavioral events is a change in the release or effectiveness of one or more neurotransmitters. Dopaminergic drugs have long been known to facilitate masculine sexual function clinically, and we have shown that the MPOA is a major site at which they facilitate male rat sexual behavior. Testosterone increases the enzyme (nitric oxide synthase, NOS) that produces nitric oxide (NO). NO maintains normal basal levels of extracellular dopamine and also an increase in dopamine in response to a female.
We recently showed that glutamate, too, is released in response to a female, and preliminary data suggest that this response also depends on testosterone. Furthermore, increasing glutamate in the MPOA facilitates sexual behavior.
References:
Dominguez et al., in press
Hull et al., 1986, 1995, 1999
Lorrain et al., 1996
Putnam et al., 2003, 2005
Sato et al., 2005
How does NO affect cellular function in the MPOA?
A major intracellular effector for NO is cGMP. We have shown that an analog of cGMP (8-Br-cGMP) in the MPOA facilitates, and blocking cGMP (with ODQ) impairs, male sexual behavior. Furthermore, cGMP is “downstream” from NO: The dopamine increase elicited by an NO donor (SNP) was blocked by a guanylyl cyclase antagonist (ODQ), but a NOS inhibitor (L-NMMA) did not block the effects of the cGMP analog.
Reference:
Sato & Hull, in press
How does the MPOA “know” that there is a receptive female near?
The major input to the MPOA is from the medial amygdala, which processes both olfactory and somatosensory information relevant for sex. Lesions of the medial amygdala impair copulation and block the MPOA dopamine increase in response to the female, but these lesions do not affect basal levels of dopamine. A dopamine agonist, microinjected into the MPOA, restores copulation to normal in animals with amygdala lesions. Furthermore, stimulation of the medial amygdala increases dopamine release in the MPOA similarly to the response to a receptive female. Therefore, the major signal to the MPOA that a receptive female is near is an increase in MPOA dopamine, mediated by the medial amygdala.
However, there are no dopamine neurons in the medial amygdala of rats, so the increase is probably mediated by glutamatergic axons either directly or indirectly from the medial amygdala to the MPOA. Dr. Juan Dominguez has demonstrated such neurons during a previous post-doctoral fellowship. Indeed, reverse dialysis of glutamate into the MPOA increases dopamine release, which depends on NO. Also, glutamate is released in the MPOA, in parallel with dopamine, before and during copulation.
References:
Dominguez et al., 2001a, b; 2004
Effects of sexual experience: From dud to stud.
Sexually experienced males copulate more efficiently and are more resistant to the effects on copulation of various lesions and stressors. We have shown that blocking either NO production or glutamate NMDA receptors in the MPOA blocks the facilitative effects of pre-exposure to a receptive female.
References:
Lagoda et al., 2004
Powell et al., 2003
Vigdorchik et al., 2003
Effects of orexin/hypocretin on male sexual behavior
Orexin/hypocretin (ORX) is a neuropeptide that is better known for its facilitation of eating and wakefulness. However, another lab has shown that microinjections of ORX into the MPOA facilitates male sexual behavior. We have now shown that ORX neurons in the lateral hypothalamus are activated (have increased immunoreactivity to Fos) by copulation and that castration decreases the number of ORX neurons. In addition, John Muschamp, a graduate student in our lab, collaborated with researchers in Buffalo, NY, to show that ORX stimulates firing of dopaminergic cells in the ventral tegmental area (the “headwaters” of the mesolimbic dopamine system). He is currently using microdialysis to test whether similar microinjections increase dopamine levels in the nucleus accumbens, the major terminus of the mesolimbic tract.
Reference:
Muschamp et al., 2004