Neurosteroids, GABAA receptors, and escalated aggressive behavior

Miczek, Klaus A.; Fish, Eric W.; Bold, Joseph F De

doi:10.1016/j.yhbeh.2003.04.002

Cited by 162 publications

(114 citation statements)

References 174 publications

Supporting

Mentioning

105

Contrasting

Unclassified

Order By: Relevance

“…3α,5α-THP administration to mice reduces alcohol-induced aggression (Miczek et al, 2003). Preliminary data from our laboratory demonstrate that resident, wild-type, female mice that are administered P (1 mg/kg s.c.), made fewer aggressive overtures toward an intruder (∼2) than did vehicle-administered mice (∼6).…”

Section: α5α-thp and Aggressionmentioning

confidence: 86%

“…In adults, increases in 3α,5α-THP in response to acute cold-water swim, shock, ether, and/or carbon dioxide exposure have been demonstrated in intact, gonadectomized, and/or adrenalectomized animals (Paul and Purdy, 1992). More subtle stimuli, such as social challenge and/or mating, also alters neurosteroidogenesis (Frye and Bayon, 1999;Frye, 2001;Miczek et al, 2003). Increases in 3α,5α-THP produced by such experiences are conserved across species, enhance GBR function, produce anxiolysis, and attenuate activation of sympathetic/hypothalamic-pituitaryadrenal (HPA) responses, which may help individuals return to a state of homeostasis following challenge (Paul and Purdy, 1992;Patchev and Almeida, 1996;Barbaccia et al, 2001;Frye 2001;Mensah-Nyagan et al, 2001).…”

Section: α5α-thp As An Important Homeostatic Regulatormentioning

confidence: 99%

“…Interestingly, hormone regimens that enhance mating typically inhibit aggression, increase exploration, and produce anti-anxiety effects (DeBold and Miczek, 1981;Frye et al, 1998). Lower dosages of 3α,5α-THP, which would be expected to produce circulating concentrations akin to that of non-receptive rodents or those approaching estrous termination, heighten aggressive behavior, whereas higher dosages are anti-aggressive and enhance lordosis (Frye, 2001;Fish et al, 2002;Miczek et al, 2003;Petralia and Frye, 2004). Circulating 3α, 5α-THP levels are naturally elevated during behavioral estrus when rats are sexuallyresponsive and show more anti-anxiety, exploratory, and pro-social behaviors (Frye et al, 2000c).…”

Section: α5α-thp As An Important Homeostatic Regulatormentioning

confidence: 99%

See 2 more Smart Citations

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

et al. 2006

View full text Add to dashboard Cite

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),...

show abstract

Section: α5α-thp and Aggressionmentioning

confidence: 86%

Section: α5α-thp As An Important Homeostatic Regulatormentioning

confidence: 99%

Section: α5α-thp As An Important Homeostatic Regulatormentioning

confidence: 99%

See 1 more Smart Citation

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

et al. 2006

View full text Add to dashboard Cite

show abstract

“…[47][48][49] Low doses of allopregnanolone increase aggressive behavior in mice, whereas higher doses decrease aggression. 50 Moreover, the addition of a low dose of progesterone to the treatment with estradiol during hormonal replacement therapy increases negative mood, but higher doses do not.…”

Section: Discussionmentioning

confidence: 99%

Progesterone selectively increases amygdala reactivity in women

et al. 2007

View full text Add to dashboard Cite

The acute neural effects of progesterone are mediated by its neuroactive metabolites allopregnanolone and pregnanolone. These neurosteroids potentiate the inhibitory actions of c-aminobutyric acid (GABA). Progesterone is known to produce anxiolytic effects in animals, but recent animal studies suggest that pregnanolone increases anxiety after a period of low allopregnanolone concentration. This effect is potentially mediated by the amygdala and related to the negative mood symptoms in humans that are observed during increased allopregnanolone levels. Therefore, we investigated with functional magnetic resonance imaging (MRI) whether a single progesterone administration to healthy young women in their follicular phase modulates the amygdala response to salient, biologically relevant stimuli. The progesterone administration increased the plasma concentrations of progesterone and allopregnanolone to levels that are reached during the luteal phase and early pregnancy. The imaging results show that progesterone selectively increased amygdala reactivity. Furthermore, functional connectivity analyses indicate that progesterone modulated functional coupling of the amygdala with distant brain regions. These results reveal a neural mechanism by which progesterone may mediate adverse effects on anxiety and mood.

show abstract

“…In animal models anxiolytic and even sedative effects of progesterone and its neuroactive metabolites have been widely reported following acute administration (Bitran et al, 1991;1995;FernandezGuasti and Picazo, 1992). However, it is worth noting that at low concentrations, which are more likely to produce plasma concentration within the physiological 13 range, these steroids can be anxiogenic or induce aggressive behaviour (Miczek et al, 2003;Gulinello and Smith, 2003).…”

Section: Discussionmentioning

confidence: 99%

A specific profile of luteal phase progesterone is associated with the development of premenstrual symptoms

Lovick

Guapo

Anselmo-Franci

et al. 2017

Psychoneuroendocrinology

View full text Add to dashboard Cite

Lovick, T., Guapo, V. G., Amselmo-Franci, J. A., Loureiro, C. M., Faleiros, C. M., Del Ben, C. M., & Brandão, M. L. (2017). A specific profile of luteal phase progesterone is associated with the development of premenstrual symptoms. Psychoneuroendocrinology, 75,[86][87][88][89][90] University of Bristol -Explore Bristol Research General rightsThis document is made available in accordance with publisher policies. Please cite only the published version using the reference above. Full terms of use are available: http://www.bristol.ac.uk/pure/about/ebr-terms There is a consensus that the development of premenstrual dysphoric states is related to cyclical change in gonadal hormone secretion during the menstrual cycle.However, results from studies seeking to link symptom severity to luteal phase progesterone concentration have been equivocal. In the present study we evaluated not only the absolute concentrations of progesterone but also the kinetics of the change in progesterone concentration in relation to development of premenstrual symptoms during the last 10 days of the luteal phase in a population of 46 healthy young adult Brazilian women aged 18-39 years, mean 26.5±6.7 years. In participants who developed symptoms of premenstrual distress, daily saliva progesterone concentration remained stable during most of the mid-late luteal phase, before declining sharply during the last 3 days prior to onset of menstruation. In contrast, progesterone concentration in asymptomatic women underwent a gradual decline over the last 8 days prior to menstruation. Neither maximum nor minimum concentrations of progesterone in the two groups were related to the appearance or severity of premenstrual symptoms. We propose that individual differences in the kinetics of progesterone secretion and/or metabolism may confer differential susceptibility to the development of premenstrual syndrome.

show abstract

Neurosteroids, GABAA receptors, and escalated aggressive behavior

Cited by 162 publications

References 174 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

Progesterone selectively increases amygdala reactivity in women

A specific profile of luteal phase progesterone is associated with the development of premenstrual symptoms

Contact Info

Product

Resources

About