Kisspeptin in the medial amygdala and sexual behavior in male rats

Gresham, Rebecca; Li, Shengyun; Adekunbi, Daniel; Hu, Miao‐Lin; Li, Xiao Feng; O’Byrne, Kevin

doi:10.1016/j.neulet.2016.05.042

Cited by 49 publications

(46 citation statements)

References 29 publications

(36 reference statements)

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“…This included the anterior and posterior cingulate, amygdala, thalamus, and globus pallidus, which are all implicated in romantic, maternal, and unconditional love [53][54][55][56] and consistent with structures known to be involved in kisspeptin signalling in humans [19,20] and rodents [10,15,21,23,24]. Interestingly, kisspeptins enhanced activation of the amygdala in response to bonding images correlated with improved positive mood [40], a Sexual behaviours -Enhances limbic and paralimbic brain activity with correlations to reward, sexual aversion, and positive mood (H) [40] -Triggers erections (R) [51] Fear -Reduces fear responses (Z) [36][37][38]43] Social behaviours -MeA kisspeptin neurone apposition with dopaminergic and vasopressinergic neurones (R) [24] Audition -Male rodent ultrasonic vocalisations increase female ARC kisspeptin activity which correlates to the duration of female searching for male (R) [34] Mood -Antidepressant-like effects (R, H) [40,44] -Anxiolytic effects (R, Z) [31,36] -Anxiogenic effects (R) [42] Olfaction -Kisspeptin anatomical framework (R, H) [24] -Kiss1r and MeA Kiss1 roles in male olfactory partner preference (R) [30,31] -Opposite-sex urinary odours stimulate RP3V and limbic kisspeptin neurones and enhance LH surge (R) [32,33] Kisspeptin signalling potential mechanism that may contribute to the desire to bond with a partner.…”

Section: Kisspeptin and Sexual Processingmentioning

confidence: 57%

“…1). Kisspeptin signalling is required for male olfactory partner preference [30], is enhanced by opposite-sex urinary odours [32,33], modulates mate preference [31], enhances auditory-reproductive behaviour [34], dampens fear responses [36], modulates anxiety [31,36,42], has antidepressant-like effects [40,44], and triggers erections [51]. Furthermore, in healthy heterosexual men, kisspeptin enhances limbic and paralimbic brain activity specifically in response to visual-evoked sexual and romantic stimuli and these enhancements correlate with behavioural measures including sexual aversion, reward, and mood [40].…”

Section: Discussionmentioning

confidence: 99%

“…Along these lines, a recent study in rodents demonstrated that direct bilateral injection of kisspeptin into the posterodorsal subnucleus of the medial amygdala dosedependently triggered multiple erections in male rats, an effect that was blocked by pretreatment with a kisspeptin antagonist (pep-234) [51]. Importantly, erections were not observed when kisspeptin was injected into the lateral cerebral ventricle suggesting a direct effect of kisspeptin at the site of the amygdala.…”

Section: Kisspeptin and Sexual Processingmentioning

confidence: 99%

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Emerging Roles of Kisspeptin in Sexual and Emotional Brain Processing

Comninos

Dhillo

2017

Neuroendocrinology

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The emergence of kisspeptin as a crucial regulator of the hypothalamo-pituitary-gonadal (HPG) axis over the last 14 years has answered many questions as to the control of reproductive hormone secretion from the hypothalamus. More recently, the role of kisspeptin outside the HPG axis has received increasing attention in the hope of delineating the pathways linking various sensory and social behaviours to reproduction. These studies, in a range of species from zebrafish to humans, have identified a role for kisspeptin in behavioural networks related to reproduction including olfaction, audition, fear, anxiety, mood, and sexual arousal. The available evidence suggests that extrahypothalamic kisspeptin signalling encourages positive aspects of emotional and sexual brain processing in a presumed drive towards reproduction and ultimately maintenance of the species at a population level. In this review, we examine these studies, which collectively propose that kisspeptin may integrate sexual and emotional brain processing with the control of the HPG axis.

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Section: Kisspeptin and Sexual Processingmentioning

confidence: 57%

Section: Discussionmentioning

confidence: 99%

Section: Kisspeptin and Sexual Processingmentioning

confidence: 99%

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Emerging Roles of Kisspeptin in Sexual and Emotional Brain Processing

Comninos

Dhillo

2017

Neuroendocrinology

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“…Recent studies have identified MeA Kiss neurons and the POA as regulators of sexual motivation and behaviour in male rodents [15, 16, 44]. Several studies have identified various neuronal types in the POA as key players in mediating male-typical mating and paternal behaviour including neurons expressing oestrogen receptor alpha [45], progesterone receptor [46], and galanin [47].…”

Section: Discussionmentioning

confidence: 99%

“…Chemogenetic activation of MeA Kiss neurons reduces anxiety and enhances the preference for oestrous females in male mice [15]. Intra-MeA infusions of kisspeptin impact LH levels and lead to increased numbers of ex-copula erections in male rats [16], suggesting that MeA Kiss signalling regulates GnRH release and participates in sexual arousal. However, Kiss1r expression has not been identified in MeA Kiss neurons, therefore it remains unclear whether MeA Kiss neurons directly regulate these responses or whether another neuronal population is involved.…”

Section: Introductionmentioning

confidence: 99%

Medial Amygdala <b><i>Kiss1</i></b> Neurons Mediate Female Pheromone Stimulation of Luteinizing Hormone in Male Mice

et al. 2018

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Background/Aims: The medial amygdala (MeA) responds to olfactory stimuli and alters reproductive physiology. However, the neuronal circuit that relays signals from the MeA to the reproductive axis remains poorly defined. This study aimed to test whether MeA kisspeptin (MeA^Kiss) neurons in male mice are sensitive to sexually relevant olfactory stimuli and transmit signals to alter reproductive physiology. We also investigated whether MeA^Kiss neurons have the capacity to elaborate glutamate and GABA neurotransmitters and potentially contribute to reproductive axis regulation. Methods: Using female urine as a pheromone stimulus, MeA^Kiss neuronal activity was analysed and serum luteinizing hormone (LH) was measured in male mice. Next, using a chemogenetic approach, MeA^Kiss neurons were bi-directionally modulated to measure the effect on serum LH and evaluate the activation of the preoptic area. Lastly, using in situ hybridization, we identified the proportion of MeA^Kiss neurons that express markers for GABAergic (Vgat) and glutamatergic (Vglut2) neurotransmission. Results: Male mice exposed to female urine showed a two-fold increase in the number of c-Fos-positive MeA^Kiss neurons concomitant with raised LH. Chemogenetic activation of MeA^Kiss neurons significantly increased LH in the absence of urine exposure, whereas inhibition of MeA^Kiss neurons did not alter LH. In situ hybridization revealed that MeA^Kiss neurons are a mixed neuronal population in which 71% express Vgat mRNA, 29% express Vglut2 mRNA, and 6% express both. Conclusions: Our results uncover, for the first time, that MeA^Kiss neurons process sexually relevant olfactory signals to influence reproductive hormone levels in male mice, likely through a complex interplay of neuropeptide and neurotransmitter signalling.

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Effects of Kisspeptin Administration in Women With Hypoactive Sexual Desire Disorder

et al. 2022

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ImportanceDespite being the most common female sexual health complaint worldwide, current treatment options for hypoactive sexual desire disorder (HSDD) are limited in their safety and effectiveness. The hormone kisspeptin is a key endogenous activator of the reproductive hormonal axis with additional emerging roles in sexual and emotional behavior; however, its effects in women with HSDD are unknown.ObjectiveTo test the hypothesis that kisspeptin enhances sexual and attraction brain processing in women with HSDD.Design, Setting, and ParticipantsThis randomized clinical trial was double-masked and placebo controlled with a 2-way crossover. The trial was conducted in a university research setting in the UK from October 2020 to April 2021. Eligible participants were premenopausal women with HSDD. Functional neuroimaging, psychometric, and hormonal analyses were employed to investigate the effects of kisspeptin administration on brain processing, in response to erotic stimuli (erotic videos) and facial attraction (face images of varying attractiveness). Data were analyzed from May to December 2021.InterventionsA 75-minute intravenous infusion of kisspeptin-54 (1 nmol/kg/h) vs equivalent-rate placebo infusion.Main Outcomes and MeasuresBlood oxygen level–dependent responses across the whole brain and regions of interest during kisspeptin vs placebo administration in response to erotic and facial attraction stimuli.ResultsOf the 40 participants who were randomized, 32 women completed both kisspeptin and placebo visits, with a mean (SE) age of 29.2 (1.2) years. Kisspeptin administration resulted in modulations in sexual and facial attraction brain processing (deactivation of the left inferior frontal gyrus: Z max, 3.76; P = .01; activation of the right postcentral and supramarginal gyrus: Z max, 3.73; P &lt; .001; deactivation of the right temporoparietal junction: Z max 4.08; P = .02). Furthermore, positive correlations were observed between kisspeptin-enhanced hippocampal activity in response to erotic videos, and baseline distress relating to sexual function (r = 0.469; P = .007). Kisspeptin’s enhancement of posterior cingulate cortex activity in response to attractive male faces also correlated with reduced sexual aversion, providing additional functional significance (r = 0.476, P = .005). Kisspeptin was well-tolerated with no reported adverse effects.Conclusions and RelevanceThese findings lay the foundations for clinical applications for kisspeptin in women with HSDD.Trial RegistrationISRCTN trial registry identifier: ISRCTN17271094

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Kisspeptin in the medial amygdala and sexual behavior in male rats

Abstract: HighlightsKisspeptin in the posterodorsal medial amygdala evokes ex-copular erections in rats.The mechanism is kisspeptin receptor specific.Kisspeptin induced GnRH and LH release are not implicated.

Cited by 49 publications

References 29 publications

Emerging Roles of Kisspeptin in Sexual and Emotional Brain Processing

Emerging Roles of Kisspeptin in Sexual and Emotional Brain Processing

Medial Amygdala <b><i>Kiss1</i></b> Neurons Mediate Female Pheromone Stimulation of Luteinizing Hormone in Male Mice

Effects of Kisspeptin Administration in Women With Hypoactive Sexual Desire Disorder

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