Gossman Kyle Richard, Lowe Camryn Serra, Kirckof Adrianna, Vanmeerhaeghe Sydney, Smith Adam Steven
Department of Pharmacology and Toxicology, University of Kansas, Lawrence, KS, United States.
Program in Neuroscience, University of Kansas, Lawrence, KS, United States.
Front Neurosci. 2024 Jul 23;18:1430447. doi: 10.3389/fnins.2024.1430447. eCollection 2024.
The mesolimbic reward system is associated with the promotion and rewarding benefits of social relationships. In the socially monogamous prairie vole (), the establishment of a pair bond can be displayed by a robust preference for a breeding partner and aggressive rejection of unfamiliar conspecifics. Mesolimbic dopamine signaling influences bond-related behaviors within the vole through dopamine transmission and receptor activity in the nucleus accumbens. However, only one experiment has examined how the ventral tegmental area (VTA), a region that produces much of the fore- and mid-brain dopamine, regulates these social behaviors. Specifically, inhibition of either glutamate or GABA neurons in the VTA during a brief courtship promoted a partner preference formation in male prairie voles. The VTA is a heterogeneous structure that contains dopamine, GABA, and glutamate neurons as well as receives a variety of projections including corticotropin-releasing factor (CRF) suggested to modulate dopamine release.
We used pharmacological manipulation to examine how GABA and CRF signaling in the VTA modulate partner preference formation in male and female prairie voles. Specifically, we used a 3 h partner preference test, a social choice test, to assess the formation of a partner preference following an infused bicuculline and CRF during a 1 h cohabitation and muscimol and CP154526, a CRFR1 antagonist, during a 24 h cohabitation with an opposite-sex conspecific.
Our study demonstrated that bicuculline, a GABA receptor antagonist, and CRF in the VTA promoted a partner preference, whereas low-dose muscimol, a GABA receptor agonist, and CP154526, a CRFR1 antagonist, inhibited a partner preference in both male and female prairie voles.
This study demonstrated that GABA and CRF inputs into the VTA is necessary for the formation of a partner preference in male and female prairie voles.
中脑边缘奖赏系统与社交关系的促进和奖赏益处相关。在实行社会一夫一妻制的草原田鼠中，配偶关系的建立表现为对繁殖伴侣的强烈偏好以及对陌生同种个体的攻击性排斥。中脑边缘多巴胺信号通过伏隔核中的多巴胺传递和受体活性影响田鼠体内与配偶关系相关的行为。然而，仅有一项实验研究了腹侧被盖区（VTA）这个产生大部分前脑和中脑多巴胺的区域是如何调节这些社会行为的。具体而言，在短暂求偶期间抑制VTA中的谷氨酸能或GABA能神经元可促进雄性草原田鼠形成配偶偏好。VTA是一个异质性结构，包含多巴胺能、GABA能和谷氨酸能神经元，并且接收包括促肾上腺皮质激素释放因子（CRF）在内的多种投射，这些投射被认为可调节多巴胺释放。
我们使用药理学操作来研究VTA中的GABA和CRF信号如何调节雄性和雌性草原田鼠的配偶偏好形成。具体来说，我们使用了一个3小时的配偶偏好测试，即一种社会选择测试，来评估在1小时同居期间注入荷包牡丹碱和CRF，以及在与异性同种个体24小时同居期间注入蝇蕈醇和CRFR1拮抗剂CP154526后配偶偏好的形成情况。
我们的研究表明，VTA中的GABA受体拮抗剂荷包牡丹碱和CRF可促进配偶偏好，而低剂量的GABA受体激动剂蝇蕈醇和CRFR1拮抗剂CP154526则抑制雄性和雌性草原田鼠的配偶偏好。
本研究表明，VTA中GABA和CRF的输入对于雄性和雌性草原田鼠配偶偏好的形成是必要的。
