Effects of manipulating progesterone and NMDA receptors in the ventral tegmental area for lordosis of hamsters and rats

Frye, Cheryl A.; Marrone, Jennifer A.; Walf, Alicia A.

doi:10.1007/s00213-008-1143-6

Cited by 5 publications

(7 citation statements)

References 43 publications

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“…In particular, pregnane neurosteroids can increase the potency of glutamate and glycine on their cognate receptors (Johansson and Le Grevès 2005; Malayev et al 2002). We have previously demonstrated that intra-VTA blockade of NMDARs can enhance rodent engagement in lordosis (Frye et al 2008a; Petralia et al 2007). The current findings confirm and extend these reports to demonstrate enhanced motivation to engage in copulation, as indicated by increased pacing of sexual contacts among partially ADX rats (commensurate with observations in adrenally intact rats in Table 2) and an increased proportion of MK-801-infused rats engaging in mating compared to other groups.…”

Section: Discussionmentioning

confidence: 99%

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

Frye

Paris

2010

Psychopharmacology

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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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Section: Discussionmentioning

confidence: 99%

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

Frye

Paris

2010

Psychopharmacology

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“…Considering that DA signaling, but not PR action, in the VTA is required for lordosis (Frye and Vongher, 1999; Sumida et al, 2005), these findings support the idea that PGRMC1 plays a role. However, this is likely to be a complicated story because NMDA signaling in the VTA suppresses lordosis quotients under some circumstances (Frye et al, 2008). Thus, if PGRMC1 is part of the signaling mechanism that controls lordosis, it may be involved in turning off the behavior.…”

Section: Possible Roles For Pgrmc1 In Regulating Rapid Neuroendocrinementioning

confidence: 99%

Novel progesterone receptors: neural localization and possible functions

Petersen¹,

Intlekofer²,

Moura-Conlon³

et al. 2013

Front. Neurosci.

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Progesterone (P4) regulates a wide range of neural functions and likely acts through multiple receptors. Over the past 30 years, most studies investigating neural effects of P4 focused on genomic and non-genomic actions of the classical progestin receptor (PGR). More recently the focus has widened to include two groups of non-classical P4 signaling molecules. Members of the Class II progestin and adipoQ receptor (PAQR) family are called membrane progestin receptors (mPRs) and include: mPRα (PAQR7), mPRβ (PAQR8), mPRγ (PAQR5), mPRδ (PAQR6), and mPRε (PAQR9). Members of the b5-like heme/steroid-binding protein family include progesterone receptor membrane component 1 (PGRMC1), PGRMC2, neudesin, and neuferricin. Results of our recent mapping studies show that members of the PGRMC1/S2R family, but not mPRs, are quite abundant in forebrain structures important for neuroendocrine regulation and other non-genomic effects of P4. Herein we describe the structures, neuroanatomical localization, and signaling mechanisms of these molecules. We also discuss possible roles for Pgrmc1/S2R in gonadotropin release, feminine sexual behaviors, fluid balance and neuroprotection, as well as catamenial epilepsy.

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“…In the VTA, the metabolite of progesterone, 3α,5α‐THP, has actions that facilitate mating (17,18,95,96). 3α,5α‐THP is devoid of affinity for cognate, intracellular PRs, but can have agonist‐like actions at GABA receptors, dopamine type 1‐like receptors (D 1 ), and antagonist‐like actions at NMDA receptors (NMDARs) (8,40,97–100) in the VTA to facilitate mating, as described below.…”

Section: Actions Of Progestogens In the Midbrain Vta Via Nontraditionmentioning

confidence: 99%

“…Midbrain levels of glutamate are increased with progesterone administration (17,18). Antagonising NMDARs via intra‐VTA infusions of MK‐801 or LY235959 enhances progestogen‐facilitated lordosis (99,100). These data indicate that the actions of 3α,5α‐THP in the VTA may occur, in part, through its antagonist‐like actions at NMDARs.…”

Section: Actions Of Progestogens In the Midbrain Vta Via Nontraditionmentioning

confidence: 99%

Novel Substrates for, and Sources of, Progestogens for Reproduction

Frye

2011

J Neuroendocrinology

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Steroid hormones, such as progesterone (P), are typically thought of as being primarily secreted by the gonads (albeit adrenals can also be a source) and having their actions through cognate intracellular progestin receptors (PRs). Through its actions in the midbrain Ventral Tegmental Area (VTA), P mediates appetitive (exploratory, anxiety, social approach) and consummatory (social, sexual) aspects of rodents’ mating behavior (Frye et al., 2006a). However, P and its natural metabolites (“progestogens”) are produced in the midbrain VTA independent of peripheral sources and midbrain VTA of adult rodents is devoid of intracellular PRs. One approach we have used to understand P’s effects and mechanisms in the VTA for mating is manipulate P’s actions in the VTA and to examine effects on lordosis (the posture female rodents assume for mating to occur). This review focuses on the effects and mechanisms of progestogens to influence reproduction and related proce sses. Actions of P and its 5α-reduced metabolite and neurosteroid, 5α-pregnan-3α-ol-20-one (3α,5α-THP; allopregnanolone) in the midbrain VTA to facilitate mating is described. The findings that 3α,5α-THP biosynthesis in the midbrain occurs with mating are discussed. Evidence for 3α,5α-THP’s actions in the midbrain VTA via non-traditional steroid targets is summarised. The broader relevance of these actions of 3α,5α-THP, for aspects of reproduction, beyond lordosis, are summarised. Finally, the potential role of the pregnane xenobiotic receptor in mediating 3α,5α-THP biosynthesis in the midbrain is introduced.

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Effects of manipulating progesterone and NMDA receptors in the ventral tegmental area for lordosis of hamsters and rats

Cited by 5 publications

References 43 publications

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

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

Novel progesterone receptors: neural localization and possible functions

Novel Substrates for, and Sources of, Progestogens for Reproduction

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