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Effects of neurosteroid actions at N-methyl-d-aspartate and GABAA receptors in the midbrain ventral tegmental area for anxiety-like and mating behavior of female rats

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Abstract

Rationale

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.

Objectives

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.

Methods

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.

Results

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.

Conclusions

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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Acknowledgments

This work was supported by funding from the National Institute of Mental Health (MH06769801). Technical assistance provided by Danielle Llaneza, Daniel Cusher, and Eric Zhou is appreciated.

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Authors and Affiliations

  1. Department of Psychology, The University at Albany–SUNY, Life Sciences Research Building 01058, 1400 Washington Avenue, Albany, NY, 12222, USA

    Cheryl A. Frye & Jason J. Paris

  2. Department of Biological Sciences, The University at Albany–SUNY, Albany, NY, USA

    Cheryl A. Frye

  3. Center for Neuroscience Research, The University at Albany–SUNY, Albany, NY, USA

    Cheryl A. Frye

  4. Center for Life Sciences Research, The University at Albany–SUNY, Albany, NY, USA

    Cheryl A. Frye

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  1. Cheryl A. Frye
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Correspondence to Cheryl A. Frye.

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Frye, C.A., Paris, J.J. Effects of neurosteroid actions at N-methyl-d-aspartate and GABAA receptors in the midbrain ventral tegmental area for anxiety-like and mating behavior of female rats. Psychopharmacology 213, 93–103 (2011). https://doi.org/10.1007/s00213-010-2016-3

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  • DOI: https://doi.org/10.1007/s00213-010-2016-3

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