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Kisspeptin boosts male sexual appetite and reduces anxiety

Society for Endocrinology

Increased activity of the hormone, kisspeptin, enhances sexual attraction and decreases anxiety in male mice, according to new research presented today at the Society for Endocrinology annual conference in Harrogate. The study is the first to identify that kisspeptin has an important role in regulating sexual and social behaviour and may be a new target for tackling male sexual dysfunction and anxiety-related disorders.

Kisspeptin is a hormone typically associated with development during puberty and pregnancy, however, neurons responsive to kisspeptin have also been discovered in a part of the brain called the amygdala - a region central to regulating emotional and sexual behaviours, such as anxiety or social interaction. The posterodorsal medial area of the amygdala (MePD), where the kisspeptin-responsive neurons were found, is particularly associated with pheromone-related reactions, which suggests that kisspeptin may affect sexual behaviours.

To investigate the role of these MePD kisspeptin neurons in sexual behaviours, Dr Adekunbi and colleagues from King's College London used a sophisticated and precise approach to turn on the kisspeptin-responsive neurons in the MePD of male mice and assessed the effects on their social, sexual and anxiety-related behaviours. When the kisspeptin neurons were activated, male mice paid more attention to female mice and engaged in more socially interactive behaviour. They also exhibited fewer signs of anxiety in a standard test. Taken together, these findings indicate that kisspeptin-responsive neurons of the MePD are coordinating sexual motivation and anxiety behaviours in a manner that encourages sex, and therefore increases the chances of successful reproduction.

Dr Adekunbi comments, "In men, anxiety-related disorders occur in tandem with sexual dysfunction. The findings of our study suggest that activation of MePD kisspeptin neurons coordinates sexual preference and anxiety behaviour towards copulation, indicating that amygdala kisspeptin functionally promotes maximal reproductive success in the male."

Although it is unclear whether kisspeptin has a similar effect in female mice, this study highlights an important new role for kisspeptin in reproductive biology that may lead to new treatments for male sexual dysfunction and anxiety-related disorders in the future. Several studies have shown that men are more attracted to women around the time of ovulation, a behaviour that may be partly influenced by kisspeptin-responsive neurons of the MePD in humans.

Dr Adekunbi and colleagues now plan to further investigate the function of MePD kisspeptin neurons by using the same precision technology to turn them off and examine the subsequent effect on sexual and anxiety behaviours. Dr Adekunbi says, "We can speculate that kisspeptin may modulate sexual orientation but this needs further confirmation, our planned work to silence the MePD kisspeptin neurons may provide some insight into this. For example, when the neurons are inactivated, will the male mouse prefer to interact with a male mouse over a female?"

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Abstract

P321

Kisspeptin in the posterodorsal medial amygdala modulates sexual partner preference and anxiety in male mice Daniel Adekunbi1,2,3, Xiaofeng LI1, Geffen Lass1, Olufeyi Adegoke2, Shel Yeo4, William Colledge4, Stafford Lightman5, Kevin O'Byrne1 1King's College London, London, United Kingdom, 2University of Lagos, Lagos, Nigeria, 3Babcock University, Ilishan-Remo, Ogun State, Nigeria, 4University of Cambridge, Cambridge, United Kingdom, 5University of Bristol, Bristol, United Kingdom

The posterodorsal medial amygdala (MePD) is a neural site in the limbic brain involved in regulating emotional and sexual behaviours. There is however limited information on the specific neuronal cell type in the MePD functionally mediating these behaviours in rodents. The recent discovery of a significant kisspeptin neurone population in the MePD has raised interest in the possible role of kisspeptin and its cognate receptor in sexual behaviour. This study therefore tested the hypothesis that the MePD kisspeptin neurone population is involved in regulating attraction towards opposite sex conspecifics, sexual behaviour, social interaction and anxiety response by selectively stimulating these neurones using the novel pharmacosynthetic DREADDs (designer receptors exclusively activated by designer drugs) technique. Adult male Kiss-Cre mice received bilateral stereotaxic injections of a stimulatory DREADD viral construct (AAV-hSyn-DIO-hM3D(Gq)-mCherry) targeted to the MePD which were activated by intraperitoneal (i.p.) injection of clozapine-N-oxide (CNO). Socio-sexual behaviours were assessed in a counter-balanced fashion after i.p. injection of either saline or CNO (5mg/kg). Selective activation of MePD kisspeptin neurones by CNO significantly increased the time spent by male mice in investigating an oestrous female as well as duration of social interaction. Additionally, after CNO injection the mice appeared less anxious; evidenced by longer exploratory time in the open arms of the elevated plus maze. However, levels of copulatory behaviour were comparable between CNO and saline treated controls. These data indicate that DREADD-induced activation of MePD kisspeptin neurones enhances sexual partner preference in males and social interaction and decreases anxiety, suggesting a key role played by MePD kisspeptin in sexual motivation and social behaviour.

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