Brain chemical influences sexual preference in mice

Males lacking serotonin court both sexes

When courting, male mice lacking the chemical messenger serotonin don’t seem to care whether the object of their affection is female. Mice without the neurotransmitter no longer eschew the smells of other males, wooing them instead with squeaky love songs and attempts to mount them, researchers report online March 23 in Nature.

Serotonin’s surprise role in mouse courtship may lead to a deeper understanding of how brain cells control a complex behavior.

“Nobody thought that serotonin could be involved in this kind of sexual preference,” says study coauthor Zhou-Feng Chen of Washington University School of Medicine in St. Louis.   

Scientists emphasize that the male-male courtship seen in the lab isn’t equivalent to human homosexuality. And what, if anything, serotonin has to do with human sexual behavior is still an open question.

“We have to be cautious because this is work done in mice,” Chen says. “I would be extremely careful to extrapolate these results into humans. We just don’t know much about this.”

In the study, male mice that were genetically engineered to lack serotonin-producing brain cells still courted females. But when given the choice between males or females, these mice no longer reliably chose females over males. In tests where both a male and a female mating partner were present, nearly half of the serotonin-lacking males mounted the male first, report researchers led by Yi Rao of the National Institute of Biological Sciences and Peking University in Beijing.

These mice were also more likely than control mice to emit ultrasonic squeaks — a type of mouse love song — toward other males. And although male mice usually spend more time sniffing the odor of female genitals, these mice spent equal time sniffing male and female odors. Some of these signs of altered sexual behaviors could be reversed by injecting a compound into the mice that restored brain serotonin, Rao and his colleagues found.

Psychiatrist and sexual-research scientist Milton Wainberg of Columbia University says that it’s too simplistic to apply the experimental results to human sexuality. “These mice are not gay,” Wainberg says, “These mice have a disease that makes them do one behavior, which happens to be a behavior that can be thought of as a homosexual behavior, but it’s not homosexuality. It’s not being gay.”

The researchers don’t yet know whether serotonin affects sexual behavior in female mice.

The new result “opens now quite a lot of fascinating avenues,” including questions about where, when and how serotonin exerts its control over mouse sexual behavior, says Catherine Dulac, a molecular neuroscientist and Howard Hughes Medical Institute investigator at Harvard University.

Serotonin performs a wide variety of jobs by carrying messages across brain cell connections. The neurotransmitter has been linked to behaviors including feeding, sleeping and aggression. Serotonin also regulates many cognitive processes, including mood.

In humans, antidepressant drugs that increase the amount of serotonin in the brain do have some sex-related side effects. Selective serotonin reuptake inhibitors, or SSRIs, for example, can decrease libido in people. Yet there’s absolutely no evidence that the neurotransmitter has any influence on sexual orientation, Wainberg says.

Laura Sanders is the neuroscience writer. She holds a Ph.D. in molecular biology from the University of Southern California.

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