Mouse Study: Oxytocin Regulates Female Sexual Behavior

The “cuddle” hormone oxytocin may play a particularly strong role in regulating female sexual behavior, according to a new mouse study by scientists at Rockefeller University. Oxytocin is released naturally during moments of relational bonding, such as breastfeeding, childbirth, and sex.

The research, published in the journal Cell, involved genetically changing female mice in order to eliminate the oxytocin response in the prefrontal cortex. This resulted in females showing zero sexual interest in males during their peak mating cycle.

In fact, with lowered oxytocin, the females showed the same interest in males as they did in a Lego.

The reason for this is based on a newly discovered class of brain cells. “By identifying a new population of neurons activated by oxytocin, we have uncovered one way this chemical signal influences interactions between male and female mice,” said the researchers.

The study began with a search for a new type of interneuron, one that delivers messages to other neurons across relatively short distances. As part of her doctoral thesis, Miho Nakajima began creating profiles of the genes expressed in interneurons.

She discovered an intriguing protein in the cortex: a receptor that responds to oxytocin.

“This raised the question: What is this small, scattered population of interneurons doing in response to this important signal, oxytocin?” Nakajima said.

“Because oxytocin is most involved in social behaviors of females, we decided to focus our experiments on females.”

To determine how these oxytocin receptor interneurons (OxtrINs) affected behavior, she silenced only this class of interneurons and, in separate experiments, blocked the receptor’s ability to detect oxytocin in some females.

She then gave the female mice a social behavior test. They were given a choice to explore a room with a male mouse or to explore a room with an inanimate object (a plastic Lego block).

Typically, a female will choose to explore the room with the male mouse. The results were confusing: Sometimes the mice with the silenced OxtrINs showed an abnormally high interest in the Lego, and sometimes they responded normally.

This led Nakajima to suspect the influence of the female reproductive cycle. So in the next experiment, she recorded whether the female mice were in estrus, the sexually receptive phase, or diestrus, a period of sexual inactivity. This made all the difference.

Female mice in estrus showed an unusual lack of interest in the males when their receptors were silenced. They mostly chose to poke around at the Lego.

There was no effect on females in diestrus, and there was no effect if the male mouse was replaced with a female. When Nakajima tried the same experiment on males, there was also no difference.

“We don’t yet understand how, but we think oxytocin prompts mice in estrus to become interested in investigating their potential mates,” Nakajima said.

“This suggests that the social computation going on in a female mouse’s brain differs depending on the stage of her reproductive cycle.”

Source: Rockefeller University