The role of ghrelin signalling for sexual behaviour in male mice
The role of ghrelin signalling for sexual behaviour in male mice
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DOI：
10.1111/adb.12202
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发表时间：
2016-03-01
影响因子：
3.4
通讯作者：
Jerlhag, Elisabet
中科院分区：
文献类型：
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作者：
Egecioglu, Emil;Prieto-Garcia, Luna;Jerlhag, Elisabet
众所周知，胃饥饿素是一种肠脑信号，主要通过下丘脑胃饥饿素受体 (GHS-R1A) 调节能量稳态、食物摄入和食欲。此外，生长素释放肽还激活大脑中的奖赏系统，即中脑边缘多巴胺系统，从而调节成瘾药物和美味食物的奖赏特性。鉴于中脑边缘多巴胺系统要求增强成瘾药物和自然奖励（例如性行为）的特性，我们假设生长素释放肽在男性性行为中发挥重要作用，这是本研究的一个主题。在此，我们表明，生长素释放肽治疗会增加雄性小鼠的性动机和性行为，而雄性小鼠的药物抑制（使用 GHSR-1A 拮抗剂 JMV2959）或 GHS-R1A 的基因删除会降低雌性小鼠发情期的性动机和性行为。与载体治疗相比，在用 JMV2959 治疗之前用左旋多巴（多巴胺前体）进行预处理显着增加了对雌性小鼠的偏好。相反，与媒介物相比，在用 JMV2959 治疗之前用 5-羟色氨酸（5-羟色胺前体）治疗降低了性动机。在单独的实验中，我们表明，饥饿素和 GHS-R1A 拮抗作用不会影响雄激素依赖性床上用品测试中测量的女性床上用品花费的时间。总的来说，这些数据表明饥饿激素生长素释放肽及其受体是雄性小鼠正常性行为所必需的，并且生长素释放肽信号系统对性行为的影响涉及多巴胺神经传递。
Ghrelin, a gut-brain signal, is well known to regulate energy homeostasis, food intake and appetite foremost via hypothalamic ghrelin receptors (GHS-R1A). In addition, ghrelin activates the reward systems in the brain, namely the mesolimbic dopamine system, and regulates thereby the rewarding properties of addictive drugs as well as of palatable foods. Given that the mesolimbic dopamine system mandates the reinforcing properties of addictive drugs and natural rewards, such as sexual behaviour, we hypothesize that ghrelin plays an important role for male sexual behaviour, a subject for the present studies. Herein we show that ghrelin treatment increases, whereas pharmacological suppression (using the GHSR-1A antagonist JMV2959) or genetic deletion of the GHS-R1A in male mice decreases the sexual motivation for as well as sexual behaviour with female mice in oestrus. Pre-treatment with L-dopa (a dopamine precursor) prior to treatment with JMV2959 significantly increased the preference for female mouse compared with vehicle treatment. On the contrary, treatment with 5-hydroxythyptohan (a precursor for serotonin) prior to treatment with JMV2959 decreased the sexual motivation compared to vehicle. In separate experiments, we show that ghrelin and GHS-R1A antagonism do not affect the time spent over female bedding as measured in the androgen-dependent bedding test. Collectively, these data show that the hunger hormone ghrelin and its receptor are required for normal sexual behaviour in male mice and that the effects of the ghrelin signalling system on sexual behaviour involve dopamine neurotransmission.