To uncover what drives sexual behavior in animals, researchers studied the brain activity of male mice throughout the series of actions involved in sex leading up to ejaculation. Their results, publishing in the Cell Press journal Neuron on March 19, show that the intricate dance in the brain area responsible for pleasure between two chemicals—dopamine and acetylcholine—controls the progression of sexual behavior. These findings could inspire treatments for disorders like premature ejaculation.
"Sexual behavior is a complex sequence of events," says senior author Qinghua Liu of the National Institute of Biological Sciences in Beijing. "The study revealed the dynamics of how different chemicals work together in the brain to regulate the transitions through different stages of male sexual behavior."
Previous studies of male sexual behavior focused on the initiation of sexual behavior. What exactly happens in the brain during other phases of sex remained unknown, from mounting and intromission—the insertion of the penis into the vagina—to ejaculation.
The nucleus accumbens, a brain region that plays a role in reward, responds to dopamine—a chemical often associated with pleasure. To deepen this knowledge, the team injected florescent sensors that can detect neurotransmitters, the brain's chemical messengers, into the nucleus accumbens of male mice. An optic fiber would light up if the brain released dopamine and acetylcholine, a neurotransmitter known to regulate dopamine.
The researchers found that mouse brains started to release acetylcholine rhythmically prior to the mounting. About six seconds after acetylcholine release began, the brain also began releasing dopamine. During intromission, the release of acetylcholine and dopamine fluctuated rhythmically in time with the mouse's thrusting movements. For the mice that reached ejaculation, the dopamine release then slowed down significantly before quickly rising during the transition from intromission to ejaculation.
"We are able to look at these events at a very fine time resolution to understand how neurotransmitters interact with each other," says first author Ai Miyasaka, a postdoctoral fellow at the University of Tsukuba in Japan.
The researchers also found that the concentration of dopamine played an important role. During intromission, the nerve cells expressing two major dopamine receptors, D2R and D1R, were less active than usual. If the researcher artificially activated D1R cells during intromission, the mice would immediately revert back to the mounting stage. If D2R nerve cells were activated, the mice stopped engaging in sexual activity altogether.
"We uncovered the precise dopamine signaling mechanism that helps ensure that sexual behavior follows the correct sequence," Liu says.
While mice and humans have different sexual behaviors, the brain regions and neurotransmitter systems involved in sexual function might be similar, note the authors. They suggest that this research could provide new clues to treating sexual dysfunction, particularly premature ejaculation, which affects 20% to 30% of sexually active men.
"Now we have a precise understanding of how dopamine works during sex and ejaculation," Miyasaka says, "so I believe our study has opened the door to the development of clinical treatments."
