Effects of neurosteroid actions at N-methyl-D-aspartate and GABA A receptors in the midbrain ventral tegmental area for anxiety-like and mating behavior of female rats.
Effects of neurosteroid actions at N-methyl-D-aspartate and GABA A receptors in the midbrain ventral tegmental area for anxiety-like and mating behavior of female rats.
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DOI：
10.1007/s00213-010-2016-3
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发表时间：
2011-01
影响因子：
3.4
通讯作者：
Paris, Jason J.
中科院分区：
文献类型：
--
作者：
Frye, Cheryl A.;Paris, Jason J.
关键词：
在中脑腹侧被盖区（VTA），神经甾体，如孕酮代谢产物5α-胆甾烷-3 α-醇-20-酮（3α，5 α-THP）的作用可以促进交配并影响应激相关过程。3α，5 α-THP的某些作用可能通过GABAA受体（GBR）的正调节或N-甲基-D-天冬氨酸受体（NMDAR）的负调节来影响焦虑样行为;但这尚不清楚。我们的目的是评估神经类固醇和应激因素在腹侧被盖区内NMDAR和/或GBR介导的焦虑样和交配行为中的作用。雌二醇致敏的卵巢切除大鼠（部分或完全切除肾上腺（ADX））接受VTA输注溶媒、NMDAR阻滞剂（MK-801; 200 ng）或GBR拮抗剂（荷包牡丹碱，100 ng）。然后，大鼠接受VTA内载体或神经类固醇生成增强剂（N，N-二己基-2-（4-氟苯基）吲哚-3-乙酰胺，FGIN 1-27，5 μg），并评估焦虑样和性行为。完全，部分相比，ADX显着减少开放臂探索高架加迷宫，比例的女性，从事交配，脊柱前凸的冲动，起搏的性接触，和防御性攻击性的男性。VTA内MK-801增强了开放臂调查和参与交配的雌性比例。MK-801或FGIN 1-27的输注增强了脊柱前凸，并且当共同给药时，FGIN 1-27减弱了MK-801的脊柱前凸增强作用。在FGIN 1-27之前，VTA内输注荷包牡丹碱可阻断FGIN 1-27增强脊柱前凸的作用。总之，这些数据表明，腹侧被盖区NMDAR活性的降低可能会影响探索和参与性行为的动机。这些数据表明，在腹侧被盖区的NMDAR和GBR的神经类固醇的行动是重要的探索和/或性行为。
In the midbrain ventral tegmental area (VTA), actions of neurosteroids, such as the progesterone metabolite, 5α-pregnan-3α-ol-20-one (3α,5α-THP), can facilitate mating and influence stress-related processes. Some actions of 3α,5α-THP may occur via positive modulation of GABAA receptors (GBRs), or negative modulation of N-methyl-D-aspartate receptors (NMDARs), to influence anxiety-like behavior; but this is not known. We aimed to assess the role that neurosteroids and stress factors play on intra-VTA NMDAR- and/or GBR-mediated anxiety-like and mating behavior. Estradiol-primed, ovariectomized rats, which were partially or completely adrenalectomized (ADX), received infusions of vehicle, an NMDAR blocker (MK-801; 200 ng), or a GBR antagonist (bicuculline, 100 ng) to the VTA. Rats then received intra-VTA vehicle or a neurosteroidogenesis enhancer (N,N-Dihexyl-2-(4-fluorophenyl)indole-3-acetamide, FGIN 1-27, 5 μg) and anxiety-like and sexual behavior was assessed. Complete, compared to partial, ADX significantly reduced open arm exploration on an elevated plus maze, the proportion of females that engaged in mating, lordosis quotients, pacing of sexual contacts, and defensive aggression towards a sexually vigorous male. Intra-VTA MK-801 enhanced open arm investigation and the proportion of females that engaged in mating. Infusions of either, MK-801 or FGIN 1-27, enhanced lordosis and, when co-administered, FGIN 1-27 attenuated MK-801’s lordosis-enhancing effects. Intra-VTA infusions of bicuculline, prior to FGIN 1-27, blocked FGIN 1-27’s effects to enhance lordosis. Together, these data suggest that reduced NMDAR activity in the VTA may influence motivation to explore and engage in sexual behavior. These data suggest that neurosteroid actions at NMDARs and GBRs in the VTA are important for exploration and/or sexual behavior.
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影响因子：
3.6
作者：
Frye, Cheryl A.;Paris, Jason J.
通讯作者：
Paris, Jason J.
影响因子：
3.6
作者：
Frye, C. A.;Paris, J. J.;Rhodes, M. E.
通讯作者：
Rhodes, M. E.
影响因子：
3.8
作者：
Frye, Cheryl A.;Paris, Jason J.;Rhodes, Madeline E.
通讯作者：
Rhodes, Madeline E.
影响因子：
56.9
作者：
MAJEWSKA, MD;HARRISON, NL;PAUL, SM
通讯作者：
PAUL, SM
影响因子：
3.3
作者：
通讯作者：
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