Increasing 3α,5α-THP following inhibition of neurosteroid biosynthesis in the ventral tegmental area reinstates anti-anxiety, social, and sexual behavior of naturally receptive rats
Increasing 3α,5α-THP following inhibition of neurosteroid biosynthesis in the ventral tegmental area reinstates anti-anxiety, social, and sexual behavior of naturally receptive rats
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DOI：
10.1530/rep-08-0250
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发表时间：
2009-01-01
期刊：
影响因子：
3.8
通讯作者：
Rhodes, Madeline E.
中科院分区：
文献类型：
--
作者：
Frye, Cheryl A.;Paris, Jason J.;Rhodes, Madeline E.
孕酮代谢物和神经类固醇，5 α-胆甾烷-3 α-醇-20-酮（3 α，5 α-THP），在中脑腹侧被盖区（VTA）的行动，以调节脊柱前凸，但其对其他生殖相关行为的影响还没有得到很好的理解。在中脑VTA中研究了3 α，5 α-THP形成的抑制以及3 α，5 α-THP增强对探索、焦虑和社会行为的影响。天然性接受的雌性大鼠（n = 8-10只/组）接受针对中脑VTA的媒介物、PK 11195（神经类固醇生成的抑制剂）和/或吲哚美辛（由激素原形成3 α，5 α-THP的抑制剂）的输注，并且随后输注媒介物或FGIN 1-27（神经类固醇生成增强剂）。然后在行为电池中对大鼠进行评估，该电池检查探索（开放领域），焦虑（高架迷宫），社会（社会互动）和性（节奏交配）行为。抑制3 α，5 α-THP的形成降低了探索性、抗焦虑、社交和性行为，以及中脑3 α，5 α-THP水平。在3 α，5 α-THP抑制后输注FGIN 1-27使这些行为和中脑3 α，5 α-THP水平恢复到与未施用抑制剂的对照大鼠相当的水平。这些研究结果表明，3 α，5 α-THP形成中脑腹侧被盖区可能会影响食欲，以及完善，交配行为的方面。
The progesterone metabolite and neurosteroid, 5 alpha-pregnan-3 alpha-ol-20-one (3 alpha,5 alpha-THP), has actions in the midbrain ventral tegmental area (VTA) to modulate lordosis, but its effects on other reproductively relevant behaviors are not well understood. Effects on exploration, anxiety, and social behavior resulting from inhibition of 3 alpha,5 alpha-THP formation, as well as 3 alpha,5 alpha-THP enhancement, were investigated in the midbrain VTA. Naturally sexually receptive, female rats (n = 8-10/group) received infusions aimed at the midbrain VTA of vehicle, PK11195 (an inhibitor of neurosteroidogenesis), and/or indomethacin (an inhibitor of 3 alpha,5 alpha-THP formation from prohormones), and were subsequently infused with vehicle or FGIN 1-27 (a neurosteroidogenesis enhancer). The rats were then assessed in a behavioral battery that examined exploration (open field), anxiety (elevated plus maze), social (social interaction), and sexual (paced mating) behavior. Inhibition of 3 alpha,5 alpha-THP formation decreased exploratory, anti-anxiety, social, and sexual behavior, as well as midbrain 3 alpha,5 alpha-THP levels. Infusionsof FGIN 1-27 following 3 alpha,5 alpha-THP inhibition restored these behaviors and midbrain 3 alpha,5 alpha-THP levels to those commensurate with control rats that had not been administered inhibitors. These findings suggest that 3 alpha,5 alpha-THP formation in the midbrain VTA may influence appetitive, as well as consummatory, aspects of mating behavior.