Frye Cheryl A, Qrareya Alaa, Llaneza Danielle C, Paris Jason J
Department of Psychology, The University at Albany-The State University of New York (SUNY), Albany, NY, United States.
Biological Sciences, The University at Albany-The State University of New York (SUNY), Albany, NY, United States.
Front Behav Neurosci. 2020 Feb 11;14:11. doi: 10.3389/fnbeh.2020.00011. eCollection 2020.
The neurosteroid, 5α-pregnan-3α-ol-20-one (known as "allopregnanolone" or 3α,5α-THP), is produced in the midbrain ventral tegmental area (VTA), independent of peripheral sources of progestogens, where it has potential actions at N-methyl-D-aspartate (NMDA) and GABA receptors to facilitate rodent sexual behavior. Progestogens can also have anti-anxiety effects, but whether these involve actions of centrally-derived 3α,5α-THP or these receptors to support reproductively-relevant behavior is not well understood. We investigated the extent to which 3α,5α-THP's actions NMDA and/or GABA receptors in the midbrain VTA influence reproductive behaviors. Estradiol-primed, ovariectomized/adrenalectomized (OVX/ADX) rats received midbrain VTA infusions of vehicle, an NMDA receptor blocker (MK-801; 200 ng), or a GABA receptor blocker (bicuculline; 100 ng) followed by a second infusion of vehicle or 3α,5α-THP (100 ng). Reproductively-relevant behaviors were assessed: sexual (paced mating), anxiety-like (elevated plus maze), and social (partner preference, social interaction) behavior. Compared to vehicle, intra-VTA infusions of MK-801 exerted anxiolytic-like effects on elevated plus maze behavior and enhanced lordosis. Unlike prior observations in gonadally-intact rats, intra-VTA bicuculline had no effect on the behavior of OVX/ADX rats (likely due to a floor effect). Subsequent infusions of 3α,5α-THP reversed effects on lordosis and infusions of bicuculline inhibited 3α,5α-THP-facilitated lordosis. Thus, NMDA and GABA receptors may act as mediators for reproductive behavioral effects of 3α,5α-THP in the midbrain VTA.
神经甾体5α-孕烷-3α-醇-20-酮（称为“别孕烯醇酮”或3α,5α-四氢孕酮）在中脑腹侧被盖区（VTA）产生，独立于孕激素的外周来源，它在N-甲基-D-天冬氨酸（NMDA）和GABA受体上具有潜在作用，以促进啮齿动物的性行为。孕激素也可以具有抗焦虑作用，但这些作用是否涉及中枢来源的3α,5α-四氢孕酮或这些受体以支持与生殖相关的行为尚不清楚。我们研究了中脑VTA中3α,5α-四氢孕酮对NMDA和/或GABA受体的作用在多大程度上影响生殖行为。用雌二醇预处理的去卵巢/肾上腺切除（OVX/ADX）大鼠接受中脑VTA注射溶剂、NMDA受体阻滞剂（MK-801；200 ng）或GABA受体阻滞剂（荷包牡丹碱；100 ng），随后第二次注射溶剂或3α,5α-四氢孕酮（100 ng）。评估与生殖相关的行为：性行为（有节奏交配）、焦虑样行为（高架十字迷宫）和社交行为（伴侣偏好、社交互动）。与溶剂相比，VTA内注射MK-801对高架十字迷宫行为产生抗焦虑样作用并增强脊柱前凸。与先前在性腺完整大鼠中的观察结果不同，VTA内注射荷包牡丹碱对OVX/ADX大鼠的行为没有影响（可能是由于地板效应）。随后注射3α,5α-四氢孕酮可逆转对脊柱前凸的影响，注射荷包牡丹碱可抑制3α,5α-四氢孕酮促进的脊柱前凸。因此，NMDA和GABA受体可能是3α,5α-四氢孕酮在中脑VTA中生殖行为效应的介质。
