ArticleAlcoholism, clinical and experimental research2017
Cellular GABAergic Neuroactive Steroid (3α,5α)-3-Hydroxy-Pregnan-20-One (3α,5α-THP) Immunostaining Levels Are Increased in the Ventral Tegmental Area of Human Alcohol Use Disorder Patients: A Postmortem Study.
Article in Alcoholism, clinical and experimental research, 2017. 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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Who cites it
8 citing papers in PubMed, 19 citations in OpenAlex.
- The Neuropathology of Alcohol Use Disorder: Cellular Insights From Human Post-Mortem Studies.Journal of neurochemistry · 2025Review
- The role of neurosteroids in posttraumatic stress disorder and alcohol use disorder: A review of 10 years of clinical literature and treatment implications.Frontiers in neuroendocrinology · 2024Review
- Transcriptional Dysregulation of Cholesterol Synthesis Underlies Hyposensitivity to GABA in the Ventral Tegmental Area During Acute Alcohol Withdrawal.Biological psychiatry · 2024Article
- Stress and gonadal steroid influences on alcohol drinking and withdrawal, with focus on animal models in females.Frontiers in neuroendocrinology · 2023Review
- Allopregnanolone: An overview on its synthesis and effects.Journal of neuroendocrinology · 2022Review
- Epigenetic Regulation of GABAergic Neurotransmission and Neurosteroid Biosynthesis in Alcohol Use Disorder.The international journal of neuropsychopharmacology · 2021Article
- A Rationale for Allopregnanolone Treatment of Alcohol Use Disorders: Basic and Clinical Studies.Alcoholism, clinical and experimental research · 2020Review
- Histone Deacetylase Inhibitor Suberanilohydroxamic Acid Treatment Reverses Hyposensitivity to γ-Aminobutyric Acid in the Ventral Tegmental Area During Ethanol Withdrawal.Alcoholism, clinical and experimental research · 2018Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
backgroundThe GABAergic neuroactive steroid (3α,5α)-3-hydroxy-pregnan-20-one (3α,5α-THP; allopregnanolone) enhances GABAergic activity and produces subjective effects similar to ethanol (EtOH). The effect of chronic alcohol exposure on 3α,5α-THP concentrations has been studied in mouse, rat, and monkey limbic brain areas. Chronic EtOH exposure produced divergent brain region and cell-specific changes in 3α,5α-THP concentrations in animal studies. However, 3α,5α-THP levels in similar human brain regions have never been examined in individuals diagnosed with alcohol use disorder (AUD). Therefore, we used immunohistochemistry (IHC) to examine 3α,5α-THP levels in the ventral tegmental area (VTA), substantia nigra pars medialis (SNM), and amygdala of human postmortem brains of patients diagnosed with AUD compared with social drinkers. The effects of sex and liver disease on 3α,5α-THP concentrations were examined in the aforementioned brain regions.
methodsHuman postmortem brains of AUD patients and age-matched controls were obtained from the New South Wales Brain Tissue Resource Center. IHC was performed using anti-3α,5α-THP antibody on formalin-fixed paraffin-embedded brain sections to detect cellular 3α,5α-THP levels. Immunoreactivity was analyzed by pixel density/mm
results3α,5α-THP immunoreactivity was increased by 23.2 ± 9% in the VTA of AUD patients compared with age-matched controls (p = 0.014). Moreover, a 29.6 ± 10% increase in 3α,5α-THP immunoreactivity was observed in the SNM of male AUD patients compared with male controls (p < 0.01), but not in female subjects. 3α,5α-THP immunoreactivity in the VTA and SNM regions did not differ between noncirrhotic and cirrhotic AUD patients. A sex difference in 3α,5α-THP immunoreactivity (female 51 ± 18% greater than male) was observed among control subjects in the SNM, but no other brain region. 3α,5α-THP immunoreactivity in the basolateral amygdala and lateral amygdala was negatively correlated with the length of the tissue fixation time as well as the age of the subjects, precluding assessment of the effect of AUD.
conclusionsCellular 3α,5α-THP levels in VTA are increased in human AUD patients, an effect that is likely independent of sex and liver disease. The differences between animal models and human studies should be factored into the interpretation of the physiological significance of elevated 3α,5α-THP levels in humans.
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