Effects of olanzapine infusions to the ventral tegmental area on lordosis and midbrain 3?,5?-THP concentrations in rats

Frye, Cheryl A.; Seliga, Angela

doi:10.1007/s00213-003-1523-x

Cited by 16 publications

(14 citation statements)

References 47 publications

(53 reference statements)

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“…Mice deficient in 5α-R, when administered P, do not demonstrate enhanced social and/or affective behaviors as do their wild-type counterparts . Enhancing activity of these metabolism enzymes in the VTA facilitates lordosis and formation of 3α,5α-THP (Mellon and Griffin, 2002;Frye and Seliga, 2003). These data suggest that metabolism of P to 3α,5α-THP in the VTA is essential for facilitation of lordosis.…”

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

confidence: 79%

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

confidence: 79%

“…In animal models of schizophrenia, social isolation of mice decreases 3α,5α-THP levels . The atypical antipsychotic, olanzapine, increases 3α,5α-THP levels and enhances social and affective behavior of rodents (Frye and Seliga, 2003). Thus, 3α,5α-THP may have an important role in schizoaffective disorders.…”

Section: α5α-thp and Schizoaffective Disordersmentioning

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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“…Administering P or 3α, 5α-THP systemically, to the hypothalamus, and/or midbrain, facilitates lordosis behavior of ovx, E 2 -primed rodents (Frye, 2001a,b;Frye and Gardiner, 1996;Vongher, 1999c,d, 2001;Frye et al, 2004). Experimental manipulations that increase 3α,5α-THP, independent of P levels in midbrain, are sufficient to enhance lordosis (Frye, 2001a,b;Frye et al, , 2004Frye and Petralia, 2003a,b;Frye and Seliga, 2003). Inhibiting P's metabolism to 3α,5α-THP by systemic or intra-VTA infusions of metabolism inhibitors decreases lordosis commensurate with lowering 3α,5α-THP levels (Frye and Vongher, 2001;Frye et al, 1998;Petralia et al, 2001;).…”

Section: Progestins and Lordosismentioning

confidence: 99%

Progestins influence motivation, reward, conditioning, stress, and/or response to drugs of abuse

Frye

2007

Pharmacology Biochemistry and Behavior

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Progesterone (pregn-4-ene-3,20-dione; P) and its metabolite 5α-pregnan-3α-ol-20-one (3α,5α-THP) are secreted by ovaries, adrenals, and glial cells. 3α,5α-THP in the midbrain ventral tegmental area mediates sexual receptivity of rodents through its actions at GABA A , NMDA, and/ or D 1 receptors. The extent to which 3α,5α-THP may influence anti-anxiety/anti-stress effects, conditioning and/or reward through these substrates and/or by altering hypothalamic pituitary adrenal axis function is discussed. Biosynthesis of 3α,5α-THP occurs in responses to mating and may underlie some of the rewarding aspects of sexual behavior. Recent findings from our laboratory which demonstrate that progestins can enhance approach to novel stimuli, conditioning, and reinforcement are reviewed. How progestins' effects on these processes may underlie response to drugs of abuse is considered and new findings which demonstrate interactions between progestins and cocaine are presented.

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“…Unilateral VTA infusions were administered, at a rate of 1 μl/min in awake animals (Frye and Seliga 2003), through a 30-gauge needle attached to PE-20 tubing and a 5-μl Hamilton syringe. The infusion needle was left in place for 60 s following infusion of the infusate.…”

Section: Intracranial Infusionsmentioning

confidence: 99%

In the ventral tegmental area picrotoxin blocks FGIN 1-27-induced increases in sexual behavior of rats and hamsters

Petralia

Frye

2004

Psychopharmacology

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Effects of olanzapine infusions to the ventral tegmental area on lordosis and midbrain 3?,5?-THP concentrations in rats

Abstract: Olanzapine increases lordosis and midbrain 3alpha,5alpha-THP when infused to the VTA which suggest that olanzapine's behavioral effects may result, in part, through actions of 3alpha,5alpha-THP, independent of progesterone or corticosterone.

Cited by 16 publications

References 47 publications

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

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

Progestins influence motivation, reward, conditioning, stress, and/or response to drugs of abuse

In the ventral tegmental area picrotoxin blocks FGIN 1-27-induced increases in sexual behavior of rats and hamsters

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