Institute of Neuroscience and Physiology, Department of Pharmacology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
Institute of Neuroscience and Physiology, Department of Pharmacology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden.
Horm Behav. 2020 Aug;124:104778. doi: 10.1016/j.yhbeh.2020.104778. Epub 2020 May 31.
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.
除了减少食物摄入和控制能量平衡外，胰高血糖素样肽-1（GLP-1）还抑制美味食物和成瘾药物的强化特性。这种奖励的减少涉及到在处理自然和人工奖励的区域内激活 GLP-1 受体（GLP-1R），包括外侧隔核（LDTg）、腹侧被盖区（VTA）和伏隔核壳（NAc 壳）。这些区域是介导成瘾药物和自然奖励（包括性行为）奖励的神经回路的一部分。雄性与雌性的性接触包括三个不同阶段：有社交行为的前性互动阶段，接着是雌性的交配和插入的性互动阶段，最后是以自我修饰行为为特征的后性互动阶段。尽管 GLP-1 调节奖励，但 GLP-1R 激活对性互动的影响尚不清楚。因此，我们在性经验不足的雄性小鼠的奖励神经回路的亚区中注入 GLP-1R 激动剂 Exendin-4（Ex4），并记录它们与发情雌性的新的互动。我们发现，将 Ex4 注入 LDTg、后 VTA 或 NAc 壳会减少前性互动行为，而 LDTg 或后 VTA 中 GLP-1R 的激活会减少性互动行为。相反，将 Ex4 注入前 VTA 不会影响这些行为。此外，上述区域中 GLP-1R 的激活不会影响自我修饰行为。这些数据突出表明，奖励相关区域中 GLP-1R 的激活减少了性互动链的不同方面，并进一步支持 GLP-1R 在社交行为中的作用。
