Kisspeptin neurones in the posterodorsal medial amygdala modulate sexual partner preference and anxiety in male mice.

Kisspeptin neurones in the posterodorsal medial amygdala modulate sexual partner preference and anxiety in male mice.
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DOI:
10.1111/jne.12572
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发表时间:
2018-03
影响因子:
3.2
通讯作者:
O'Byrne KT
O'Byrne KT
中科院分区:
医学3区
文献类型:
--
作者:
Adekunbi DA;Li XF;Lass G;Shetty K;Adegoke OA;Yeo SH;Colledge WH;Lightman SL;O'Byrne KT

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后背内侧杏仁核(MePD)是大脑边缘系统中参与调节情绪和性行为的神经部位。然而,有有限的信息可在特定的神经元细胞类型的MePD功能介导这些行为的啮齿动物。最近在MePD中发现了一个重要的kisspeptin神经元群体,这引起了人们对kisspeptin及其同源受体在性行为中可能作用的兴趣。因此,本研究测试的假设,MePD kisspeptin神经元人口参与调节异性同种,性行为,社会交往和焦虑反应的吸引力,通过选择性刺激这些神经元使用新的药物合成DREADD(设计师受体专门激活设计师药物)技术。成年雄性Kiss-Cre小鼠接受靶向MePD的刺激性DREADD病毒构建体(AAV-hSyn-DIO-hM 3D(Gq)-mCherry)的双侧立体定位注射,随后通过腹膜内注射氯氮平-N-氧化物(CNO)激活。在腹膜内注射生理盐水或CNO(5 mg kg-1)后,以平衡方式评估社会性行为。CNO选择性激活MePD kisspeptin神经元显著增加了雄性小鼠在研究发情雌性时所花费的时间,以及社会互动的持续时间。此外,在CNO注射后,小鼠表现出较少的焦虑,如高架十字迷宫开放臂中较长的探索时间所示。然而,CNO和盐水处理对照之间的交配行为水平相当。这些数据表明,DREADD诱导的MePD kisspeptin神经元的激活增强了男性的性伴侣偏好和社会互动,也降低了焦虑,这表明MePD kisspeptin在性动机和社会行为中发挥了关键作用。
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 available 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. The present 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 the 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, with subsequent activation by 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 (5 mg kg‐1). Selective activation of MePD kisspeptin neurones by CNO significantly increased the time spent by male mice in investigating an oestrous female, as well as the duration of social interaction. Additionally, after CNO injection, the mice appeared less anxious, as indicated by a 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 both sexual partner preference in males and social interaction and also decreases anxiety, suggesting a key role played by MePD kisspeptin in sexual motivation and social behaviour.
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