Frye C A, Rhodes M E
Department of Psychology, The University of Albany-SUNY, Albany, NY 12222, USA.
J Neuroendocrinol. 2006 Dec;18(12):960-75. doi: 10.1111/j.1365-2826.2006.01494.x.
Sequential actions of 17beta-oestradiol (E2) and progesterone (P4) in the ventromedial hypothalamus (VMH) and ventral tegmental area (VTA) mediate sexual behaviour of female rodents. In the presence of appropriate environmental stimuli, E2 and P4 can facilitate initiation of sex behaviour (i.e. lordosis), in part through classic actions at intracellular progestin receptors in the VMH. However, the effects of P4 in the VTA to modulate lordosis involve its metabolite, 5alpha-pregnan-3alpha-ol-20-one (3alpha,5alpha-THP), which can have paracrine effects in the brain to reduce anxiety and stress. We investigated the effects of 3alpha,5alpha-THP infusions to the VTA, and a control site, the substantia nigra (SN), on exploratory, anti-anxiety, social and sexual behaviours (socio-sexual behaviours) and hormone levels in the midbrain and other regions (hippocampus, diencephalon and cortex) that may mediate these functions. Ovariectomised, rats were E2-primed (10 microg, s.c.) at 0 h and were infused with beta-cyclodextrin vehicle or 3alpha,5alpha-THP to the VTA or SN 44-48 h later. Ten minutes after infusions, rats were tested in the open field, plus maze, partner preference, social interaction and paced mating tasks, or served as nontested controls. Infusions of 3alpha,5alpha-THP to the VTA, but not the SN, increased central entries in the open field, open arm time in the plus maze, time spent in proximity to a male, duration of social interaction, incidence and intensity of lordosis, pacing, proceptivity, and anti-conflict behaviour. 3Alpha,5alpha-THP, but not vehicle, infusions to the VTA (but not the SN) also increased 3alpha,5alpha-THP levels in the midbrain, as well as the hippocampus, diencephalon and cortex. Behavioural testing increased levels of the precursor of 3alpha,5alpha-THP precursor, dihydroprogesterone (DHP). Thus, infusions of 3alpha,5alpha-THP to the VTA enhance socio-sexual behaviours and increase 3alpha,5alpha-THP levels in the hippocampus, diencephalon and cortex, and behavioural testing increases DHP levels in brain areas involved in modulating socio-sexual behaviours.
17β-雌二醇（E2）和孕酮（P4）在下丘脑腹内侧核（VMH）和腹侧被盖区（VTA）的顺序作用介导了雌性啮齿动物的性行为。在适当的环境刺激下，E2和P4可促进性行为（即脊柱前凸）的启动，部分是通过在VMH细胞内孕激素受体上的经典作用。然而，P4在VTA中调节脊柱前凸的作用涉及其代谢产物5α-孕烷-3α-醇-20-酮（3α,5α-THP），它可在大脑中产生旁分泌作用以减轻焦虑和应激。我们研究了向VTA以及作为对照部位的黑质（SN）注射3α,5α-THP对探索、抗焦虑、社交和性行为（社会性行为）以及中脑和其他可能介导这些功能的区域（海马体、间脑和皮质）中的激素水平的影响。对去卵巢大鼠在0小时皮下注射E2进行预处理（10微克），并在44 - 48小时后向VTA或SN注射β-环糊精载体或3α,5α-THP。注射后10分钟，对大鼠进行旷场试验、十字迷宫试验、伴侣偏好试验、社交互动试验和定速交配试验，或者作为未测试的对照。向VTA而非SN注射3α,5α-THP可增加旷场试验中的中央进入次数、十字迷宫试验中的开放臂停留时间、靠近雄性的时间、社交互动持续时间、脊柱前凸的发生率和强度、定速、接受性以及抗冲突行为。向VTA（而非SN）注射3α,5α-THP而非载体还可增加中脑以及海马体、间脑和皮质中的3α,5α-THP水平。行为测试可提高3α,5α-THP前体二氢孕酮（DHP）的水平。因此，向VTA注射3α,5α-THP可增强社会性行为，并增加海马体、间脑和皮质中的3α,5α-THP水平，而行为测试可提高参与调节社会性行为的脑区中的DHP水平。
