Elsevier

Hormones and Behavior

Volume 124, August 2020, 104778
Hormones and Behavior

The glucagon-like peptide-1 receptor agonist, exendin-4, reduces sexual interaction behaviors in a brain site-specific manner in sexually naïve male mice

https://doi.org/10.1016/j.yhbeh.2020.104778Get rights and content
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Highlights

  • Exendin-4 into LDTg reduces pre- and sexual interaction behaviors in sexually naïve male mice.

  • Exendin-4 into pVTA, but not aVTA, reduces pre- and sexual interaction behaviors in sexually naïve male mice.

  • In sexually naïve male mice, exendin-4 into NAc shell decreases pre-sexual interaction behaviors.

  • These findings support that GLP-1R activation reduces sexual interaction behaviors in a brain site-specific manner.

Abstract

Besides reducing food intake and controlling energy balance, glucagon-like peptide-1 (GLP-1) suppresses the reinforcing properties of palatable foods and addictive drugs. This reduction in reward involves activation of GLP-1 receptors (GLP-1R) within areas processing natural and artificial rewards, including the laterodorsal tegmental area (LDTg), ventral tegmental area (VTA) and nucleus accumbens (NAc) shell. These areas are part of a neurocircuitry mediating reward from addictive drugs and natural rewards including sexual behaviors. The male sexual encounter with a female includes three different stages: a pre-sexual interaction phase with social behaviors, which is followed by a sexual interaction phase with mounting and intromission of the female, and ends with a post-sexual interaction phase characterized by self-grooming behaviors. Albeit GLP-1 modulates reward, the influence of GLP-1R activation on sexual interaction is unknown. Thus, we infused the GLP-1R agonist, exendin-4 (Ex4), into sub-regions of the reward neurocircuitry in sexually naïve male mice and recorded their novel interaction with an estrus female. We found that Ex4 into the LDTg, posterior VTA or NAc shell reduces pre-sexual interaction behaviors and activation of GLP-1R in the LDTg or posterior VTA decreases sexual interaction behaviors. Contrarily, Ex4 infusion into anterior VTA does not influence these behaviors. Furthermore, self-grooming behaviors are not influenced by activation of GLP-1R in the aforementioned areas. These data highlight that activation of GLP-1R in reward-related areas reduces different aspects of the sexual interaction chain and further supports a role of the GLP-1R in social behaviors.

Keywords

Sexual interaction behaviors
GLP-1R
Testosterone
Corticosterone
Nucleus accumbens shell
Ventral tegmental area
Laterodorsal tegmental area
Sexually naïve male mice

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