A contributory role for midbrain progesterone in the facilitation of female sexual behavior in rats

Pleim, Eric T.; Baumann, Jane; Barfield, Ronald J.

doi:10.1016/0018-506x(91)90036-h

Cited by 44 publications

(26 citation statements)

References 19 publications

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“…Dried down tubes were reconstituted with phosphate assay buffer to the original serum volume. 2 , P 4 , DHP, and 3α,5α-THP were extracted from brain tissues following homogenization with a glass/glass homogenizer in 50% MeOH, 1% acetic acid. Tissues were centrifuged at 3000 × g and the supernatant was chromatographed on Sepak-cartridges equilibrated with 50% MeOH:1% acetic acid.…”

Section: 72mentioning

confidence: 99%

“…Systemic or intra-brain administration of E 2 and/or P 4 to the ventromedial hypothalamus (VMH) of ovariectomized rats reveals that actions of these hormones in this area are sufficient to initiate lordosis [1,2]. However, P 4 also has effects in other brain regions, such as the ventral tegmental area (VTA) to influence the duration and intensity of lordosis [3,4].…”

Section: Introductionmentioning

confidence: 99%

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Infusions of 3α,5α-THP to the VTA enhance exploratory, anti-anxiety, social, and sexual behavior and increase levels of 3α,5α-THP in midbrain, hippocampus, diencephalon, and cortex of female rats

Frye

Rhodes

2008

Behavioural Brain Research

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Abstract17β-Estradiol (E 2 ) and progesterone (P 4 ) influence the onset and duration of sexual behavior and are also associated with changes in behaviors that may contribute to mating, such as exploration, anxiety, and social behaviors (socio-sexual behaviors). In the midbrain ventral tegmental area (VTA), the P 4 metabolite, 5α-pregnan-3α-ol-20-one (3α,5α-THP), modulates lordosis of E 2 -primed rodents; 3α,5α-THP can also influence anxiety and social behaviors. To examine if 3α,5α-THP in the VTA mediates socio-sexual behaviors, we infused 3α,5α-THP to the VTA of diestrous and proestrous rats. As expected, proestrous, compared to diestrous, rats showed more exploratory (open field), anxiolytic (elevated plus maze), pro-social (partner preference, social interaction), and sexual (paced mating) behavior and had increased E 2 , P 4 , dihydroprogesterone (DHP), and 3α,5α-THP in serum, midbrain, hippocampus, diencephalon, and cortex. Infusions of 3α,5α-THP to the VTA, but not control sites, such as the substantia nigra (SN) or central grey (CG), of diestrous rats produced behavioral and endocrine effects akin to that of proestrous rats and increased DHP and 3α,5α-THP levels in midbrain, hippocampus, and diencephalon. Levels of DHP and 3α,5α-THP, but neither E 2 nor P 4 concentrations, in midbrain, hippocampus, diencephalon, and/or cortex were positively correlated with socio-sexual behaviors. Thus, 3α,5α-THP infusions to the VTA, but not SN or CG, can enhance socio-sexual behaviors and increase levels in midbrain, hippocampus, and diencephalon.

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Section: 72mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Infusions of 3α,5α-THP to the VTA enhance exploratory, anti-anxiety, social, and sexual behavior and increase levels of 3α,5α-THP in midbrain, hippocampus, diencephalon, and cortex of female rats

Frye

Rhodes

2008

Behavioural Brain Research

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“…Accumulation of 3 H P is greater in the midbrain than the hypothalamus (Whalen and Luttge, 1971). P alone to the VTA enhances lordosis or augments lordosis facilitation initiated by P implants to the hypothalamus (Pleim et al, 1991). Lesions to the VTA, or cutting connections between the VTA and hypothalamus, disrupts initiation and maintenance, respectively, of P-facilitated lordosis (Rose, 1990).…”

Section: α5α-thp's Effects and Mechanisms In The Vta For Lordosismentioning

confidence: 99%

3α-hydroxy-5α-pregnan-20-one in the midbrain ventral tegmental area mediates social, sexual, and affective behaviors

et al. 2006

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Progestins mediate the onset and duration of lordosis, the mating posture of female rodents, through actions in the hypothalamus and ventral tegmental area. In the hypothalamus, progesterone has traditional, "genomic" actions via intracellular progestin receptors. In the ventral tegmental area, 3α-hydroxy-5α-pregnan-20-one has "non-genomic" actions independent of progestin receptors to facilitate lordosis that involve GABA A /benzodiazepine receptors, NMDA type glutamate receptors, and/or dopamine receptors. 3α-Hydroxy-5α-pregnan-20-one levels also change with behavioral and/ or environmental stimuli and may have a role in other reproductively-relevant behaviors, such as affiliation, exploration, and anxiety (socio-sexual behaviors). Data are reviewed that support the notion that: 1) effects of 3α-hydroxy-5α-pregnan-20-one in the midbrain ventral tegmental area facilitate lordosis and other reproductively-relevant behaviors. 2) 3α-Hydroxy-5α-pregnan-20-one, formed in the ventral tegmental area from metabolism of progestins, produced peripherally by endocrine glands, or centrally from biosynthesis in glial cells mediates socio-sexual behaviors. 3) 3α-Hydroxy-5α-pregnan-20-one's actions at GABA A /benzodiazepine receptors, NMDA type glutamate receptors, and dopamine receptors in the ventral tegmental area are important for lordosis; however, effects at these substrates on socio-sexual behaviors have not been elucidated. Given 3α-hydroxy-5α-pregnan-20-one's involvement in stress responses, its putative role as a homeostatic regulator and in the pathophysiology and treatment of neuropsychiatric disorders is discussed. Keywords steroidogenesis; GABA A receptors; NMDA receptors; dopamine; stress response; mood Our research focuses on the mechanisms of progestins' actions in the midbrain ventral tegmental area (VTA) that mediate the onset and duration of sexual behavior of female rodents. To date, the majority of our investigations have utilized a model system in which progestins' mechanisms are manipulated in the VTA and/or the hypothalamus of ovariectomized (OVX), estrogen (E)-primed rodents. The effects on lordosis, the stereotypic posture which female * Correspondence to: C. A. Frye, Department of Psychology, Social Science 369, the University at Albany-SUNY, 1400 Washington Avenue, Albany, NY 12222, USA. Tel: +1-518-442-4836; fax: +1-518-442-4867. E-mail address: cafrye@cnsunix.albany.edu (C. A. Frye). NIH Public Access Author ManuscriptNeuroscience. Author manuscript; available in PMC 2008 September 2. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript rodents assume to enable mating to occur (given appropriate hormonal and environmental stimulation), are then used as a bioassay to indicate which mechanisms of progestins are required for lordosis. This approach has revealed that progesterone (P) has classic actions through intracellular progestin receptors (PRs-"genomic" actions) in the hypothalamus to initiate lordosis, but P's metabolite, 3α-hydroxy-5α-pregnan-20-one (3α,5α-THP),...

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“…The resulting effects on lordosis, the stereotypic posture that female rodents assume to enable mating to occur (given appropriate hormonal and environmental stimulation), are then used as a bioassay of progestins' actions. Results of lesions or progestin administration to the VMH and/or VTA of ovariectomized (ovx) rodents primed with 17β-estradiol (E 2 ) indicate that progesterone (P 4 ) has effects to initiate and modulate lordosis respectively in these regions [1][2][3][4][5][6][7]. In addition to different consequences of P 4' s actions in these regions, there is emerging evidence that P 4 has different mechanisms in the VMH and VTA to mediate lordosis.…”

Section: Introductionmentioning

confidence: 99%

Membrane actions of progestins at dopamine type 1-like and GABAA receptors involve downstream signal transduction pathways

Frye

Walf

2008

Steroids

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In the ventral tegmental area (VTA), progestins facilitate lordosis via rapid actions at membrane dopamine Type 1-like (D 1 ) and/or GABA A receptors (GBRs), rather than via cognate, intracellular progestin receptors. Downstream signal transduction pathways involved in these effects were investigated using lordosis as a bioassay. If progestins' actions at D 1 and/or GBRs in the VTA require activation of G-proteins, adenylyl cyclase, cyclic AMP-dependent protein kinase A (PKA), phospholipase C (PLC), and/or PKC, then pharmacologically blocking these pathways would be expected to attenuate progestin-facilitated lordosis and its enhancement by D 1 and GBR activity. Ovariectomized, estradiol-primed rats were infused first with vehicle or signal transduction inhibitor, and second with vehicle, a D 1 or GBR agonist, and then with vehicle or progestins to the VTA. Rats were tested for lordosis following infusions. Results indicated that initiation of G-proteins, adenylyl cyclase, PKA, PLC, or PKC in the VTA is required for rapid effects of progestins through D 1 and/ or GBRs to facilitate lordosis. As well, progestins' actions at n-methyl-d-aspartate receptors (NMDARs) may modulate activity at D 1 and/or GBRs and mitogen activated protein kinase may be a common signaling pathway. Findings from a microarray study demonstrated that there was upregulation of genes associated with steroid metabolism, GBRs, D 1 , NMDARs and signal transduction factors in the midbrain VTA of naturally-receptive mated compared to non-mated rats. Thus, in the VTA, progestins have rapid membrane-mediated actions via D 1 , GBRs, NMDARs and their downstream signal transduction pathways.

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A contributory role for midbrain progesterone in the facilitation of female sexual behavior in rats

Cited by 44 publications

References 19 publications

Infusions of 3α,5α-THP to the VTA enhance exploratory, anti-anxiety, social, and sexual behavior and increase levels of 3α,5α-THP in midbrain, hippocampus, diencephalon, and cortex of female rats

Infusions of 3α,5α-THP to the VTA enhance exploratory, anti-anxiety, social, and sexual behavior and increase levels of 3α,5α-THP in midbrain, hippocampus, diencephalon, and cortex of female rats

3α-hydroxy-5α-pregnan-20-one in the midbrain ventral tegmental area mediates social, sexual, and affective behaviors

Membrane actions of progestins at dopamine type 1-like and GABAA receptors involve downstream signal transduction pathways

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