ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2014
Ethanol alters local cellular levels of (3α,5α)-3-hydroxypregnan-20-one (3α,5α-THP) independent of the adrenals in subcortical brain regions.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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8 citing papers in PubMed, 14 citations in OpenAlex.
- Variation in AKR1C3, which encodes the neuroactive steroid synthetic enzyme 3α-HSD type 2 (17β-HSD type 5), moderates the subjective effects of alcohol.Psychopharmacology · 2014Trial
- Adolescent intermittent ethanol exposure induces sex-dependent divergent changes in ethanol drinking and motor activity in adulthood in C57BL/6J mice.Journal of neuroscience research · 2022Article
- Early postnatal allopregnanolone levels alteration and adult behavioral disruption in rats: Implication for drug abuse.Neurobiology of stress · 2020Article
- Dynamic Adaptation in Neurosteroid Networks in Response to Alcohol.Handbook of experimental pharmacology · 2018Article
- Neurosteroidogenesis Today: Novel Targets for Neuroactive Steroid Synthesis and Action and Their Relevance for Translational Research.Journal of neuroendocrinology · 2016Review
- Divergent neuroactive steroid responses to stress and ethanol in rat and mouse strains: relevance for human studies.Psychopharmacology · 2014Review
- Dihydromyricetin prevents fetal alcohol exposure-induced behavioral and physiological deficits: the roles of GABAA receptors in adolescence.Neurochemical research · 2014Article
- Overexpression of the steroidogenic enzyme cytochrome P450 side chain cleavage in the ventral tegmental area increases 3α,5α-THP and reduces long-term operant ethanol self-administration.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2014Article
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7 authors at 1 institution in 1 country.
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Abstract
The neuroactive steroid (3α,5α)-3-hydroxypregnan-20-one (3α,5α-THP or allopregnanolone) is a positive modulator of GABAA receptors synthesized in the brain, adrenal glands, and gonads. In rats, ethanol activates the hypothalamic-pituitary-adrenal axis and elevates 3α,5α-THP in plasma, cerebral cortex, and hippocampus. In vivo, these effects are dependent on both the pituitary and adrenal glands. In vitro, however, ethanol locally increases 3α,5α-THP in hippocampal slices, in the absence of adrenal influence. Therefore, it is not known whether ethanol can change local brain levels of 3α,5α-THP in vivo, independent of the adrenals. To directly address this controversy, we administered ethanol (2 g/kg) or saline to rats that underwent adrenalectomy (ADX) or received sham surgery and performed immunohistochemistry for 3α,5α-THP. In the medial prefrontal cortex (mPFC), ethanol increased 3α,5α-THP after sham surgery, compared with saline controls, with no ethanol-induced change in 3α,5α-THP following ADX. In subcortical regions, 3α,5α-THP was increased independent of adrenals in the CA1 pyramidal cell layer, dentate gyrus polymorphic layer, bed nucleus of the stria terminalis, and paraventricular nucleus of the hypothalamus. Furthermore, ethanol decreased 3α,5α-THP labeling in the nucleus accumbens shore and central nucleus of the amygdala, independent of the adrenal glands. These data indicate that ethanol dynamically regulates local 3α,5α-THP levels in several subcortical regions; however, the adrenal glands contribute to 3α,5α-THP elevations in the mPFC. Using double immunofluorescent labeling we determined that adrenal dependence of 3α,5α-THP induction by ethanol is not due to a lack of colocalization of 3α,5α-THP with the cholesterol transporters steroidogenic acute regulatory protein (StAR) or translocator protein (TSPO).
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