Biochemistry of Stress, Sexual Issues in Model Organisms

Tokyo Metropolitan University

Tokyo, Japan – Scientists from Tokyo Metropolitan University have revealed key parts of the biochemical pathways connecting stress to sexual dysfunction. By studying Drosophila fruit flies, they showed that the neurotransmitter dopamine was responsible for determining how long male flies showed persistent courtship suppression after being confined in a small space, but not whether mating was suppressed in the first place. Their findings in a key model organism illuminate neurobiological factors causing sexual dysfunction in other organisms, including humans.

The biochemistry of stress is a crucial yet poorly understood aspect of neurobiology. Exposure to internal or external stimuli is known to trigger changes in the brain which continue to affect organisms well beyond the duration of the event. An example is how stress affects sexual behavior; people who suffer from post-traumatic stress disorder are known to often exhibit sexual dysfunction. But despite robust evidence, the molecular mechanisms by which stress causes diminished sex drive are not yet understood.

A team led by Professor Takaomi Sakai of Tokyo Metropolitan University have been using the Drosophila fruit fly to study the relationship between stress and behavioral changes. Fruit flies are crucial "model organisms," whose biochemical pathways are similar enough to a vast range of animals, including mammals, to reveal key aspects of their function, while being much easier to study. The team looked at how "small-space" stress, the impact of putting male fruit flies in a confined space, led to the suppression of courtship behavior. Confinement stress is known to affect many organisms, but this was the first time it was applied to study fruit flies.

The team discovered that the duration over which male flies were stressed influenced how long the suppressed courtship behavior lasted. Flies confined for ten minutes showed no suppression, while those confined for 30 or 60 minutes revealed clearly suppressed courtship. The longer the flies were stressed, the longer the effect lasted. In fact, those subjected to 7 or 24 hours of stress showed courtship suppression for at least five days. Curiously, this wasn't simply due to reduced motility or appetite.

To trace the biochemical origins of this phenomenon, they investigated dopamine, a neurotransmitter known to be involved in responses to stress. Studying fruit flies with production of dopamine either genetically or pharmacologically suppressed, they discovered that neither showed any difference in whether courtship suppression occurred or not; however, it did significantly affect whether the stress-induced response lasted. Thus, dopamine was specifically involved in the persistence of stress-induced behavioral change. They traced this effect to the mushroom body, a part of the brain associated with sensory processing, where specific dopamine receptors were found to mediate the sustaining of stress-induced behavior.

The team's findings illuminate the specific role played by dopamine in mediating the impact of stress on sexual dysfunction. This is critical evidence for elucidating how stress affects behavior and wellbeing in other organisms, including human beings.

This work was supported by JSPS KAKENHI Grant Numbers 21H02528 and 21H00434.

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