ArticleNeuroscience2013
A stress steroid triggers anxiety via increased expression of α4βδ GABAA receptors in methamphetamine dependence.
Article in Neuroscience, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 24 citations in OpenAlex.
- Risk of Relapse Assessment Scale for Metamphetamine Abusers: Reliability and Validity Study of the Turkish Version.Psychiatry and clinical psychopharmacology · 2023Article
- Oxidative Stress and Inflammatory Biomarkers in People with Methamphetamine Use Disorder.Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology · 2023Article
- Long-Term Management of Generalised Anxiety Disorder with Low-Dose Continuous Infusions of Flumazenil: A Case Series.Behavioral sciences (Basel, Switzerland) · 2022Article
- Very low dose naltrexone in opioid detoxification: a double-blind, randomized clinical trial of efficacy and safety.Toxicological research · 2020Article
- Pubertal hormones increase hippocampal expression of α4βδ GABANeuroscience letters · 2019Article
- Role of Prefrontal Serotonergic and Dopaminergic Systems in Encounter-Induced Hyperactivity in Methamphetamine-Sensitized Mice.The international journal of neuropsychopharmacology · 2017Article
- Anxiety level and correlates in methamphetamine-dependent patients during acute withdrawal.Medicine · 2017Article
- Fragment C Domain of Tetanus Toxin Mitigates Methamphetamine Neurotoxicity and Its Motor Consequences in Mice.The international journal of neuropsychopharmacology · 2016Article
- Flumazenil decreases surface expression of α4β2δ GABAA receptors by increasing the rate of receptor internalization.Brain research bulletin · 2016Article
- On Gelsemium and Complementary and Alternative Medicine (CAM) in Anxiety and Experimental Neurology.Neurology and therapy · 2015Article
- Characterization of neurosteroid effects on hyperpolarizing current at α4β2δ GABAA receptors.Psychopharmacology · 2014Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Methamphetamine (METH) is an addictive stimulant drug. In addition to drug craving and lethargy, METH withdrawal is associated with stress-triggered anxiety. However, the cellular basis for this stress-triggered anxiety is not understood. The present results suggest that during METH withdrawal (24h) following chronic exposure (3mg/kg, i.p. for 3-5weeks) of adult, male mice, the effect of one neurosteroid released by stress, 3α,5α-THP (3α-OH-5α-pregnan-20-one), and its 3α,5β isomer reverse to trigger anxiety assessed by the acoustic startle response (ASR), in contrast to their usual anti-anxiety effects. This novel effect of 3α,5β-THP was due to increased (three-fold) hippocampal expression of α4βδ GABAA receptors (GABARs) during METH withdrawal (24h-4weeks) because anxiogenic effects of 3α,5β-THP were not seen in α4-/- mice. 3α,5β-THP reduces current at these receptors when it is hyperpolarizing, as observed during METH withdrawal. As a result, 3α,5β-THP (30nM) increased neuronal excitability, assessed with current clamp and cell-attached recordings in CA1hippocampus, one CNS site which regulates anxiety. α4βδ GABARs were first increased 1h after METH exposure and recovered 6weeks after METH withdrawal. Similar increases in α4βδ GABARs and anxiogenic effects of 3α,5β-THP were noted in rats during METH withdrawal (24h). In contrast, the ASR was increased by chronic METH treatment in the absence of 3α,5β-THP administration due to its stimulant effect. Although α4βδ GABARs were increased by chronic METH treatment, the GABAergic current recorded from hippocampal neurons at this time was a depolarizing, shunting inhibition, which was potentiated by 3α,5β-THP. This steroid reduced neuronal excitability and anxiety during chronic METH treatment, consistent with its typical effect. Flumazenil (10mg/kg, i.p., 3×) reduced α4βδ expression and prevented the anxiogenic effect of 3α,5β-THP after METH withdrawal. Our findings suggest a novel mechanism underlying stress-triggered anxiety after METH withdrawal mediated by α4βδ GABARs.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.