Neurosteroids in alcohol and substance use

Brett C Ginsburg, Lisa R Gerak, Lance R. McMahon, John D Roache

Research output: Chapter in Book/Report/Conference proceedingChapter

2 Citations (Scopus)

Abstract

Allopregnanolone and related neurosteroids share effects with ethanol at several critical targets. Though data are equivocal in humans, acute administration of ethanol (and several other drugs of abuse) increases brain and plasma levels of allopregnanolone in animals. Evidence exists suggesting that this effect of ethanol is mediated via the peripheral or mitochondrial benzodiazepine receptor (PBR). PBR activation can stimulate neurosteroid synthesis and results in anxiolytic effects similar to ethanol, benzodiazepines, and neurosteroids. Further, finasteride, an inhibitor of neurosteroidogenesis, blunts some effects of ethanol in animals and humans. Thus, neurosteroids may modulate or mediate effects of ethanol, benzodiazepines, and barbiturates. Like ethanol and allopregnanolone, benzodiazepines and barbiturates are positive GABA-A receptor modulators. Accordingly, neurosteroids share discriminative stimulus properties with ethanol, benzodiazepines, and barbiturates. Allopregnanolone and related neurosteroids are self-administered by animals, similar to ethanol and other abused drugs. A role for neurosteroids in ethanol tolerance and withdrawal has also emerged, as rodents undergoing ethanol withdrawal are sensitized to neurosteroid effects and alcoholics in withdrawal display reduced allopregnanolone levels. While symmetrical cross tolerance develops between ethanol and benzodiazepines, asymmetrical cross tolerance develops between neurosteroids and benzodiazepines or ethanol, which could be exploited to help treat ethanol, benzodiazepine or barbiturate dependence and withdrawal.

Original languageEnglish (US)
Title of host publicationNeuroactive Steroids in Brain Function, Behavior and Neuropsychiatric Disorders: Novel Strategies for Research and Treatment
PublisherSpringer Netherlands
Pages509-538
Number of pages30
ISBN (Print)9781402068539
DOIs
StatePublished - 2008

Fingerprint

Neurotransmitter Agents
Ethanol
Alcohols
Pregnanolone
Benzodiazepines
Barbiturates
GABA-A Receptors
Finasteride
Anti-Anxiety Agents
Street Drugs
Alcoholics
Rodentia

Keywords

  • barbiturate
  • benzodiazepine
  • cannabinoid
  • cocaine
  • drug abuse
  • Ethanol
  • GABA
  • NMDA
  • tolerance
  • withdrawal

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Ginsburg, B. C., Gerak, L. R., McMahon, L. R., & Roache, J. D. (2008). Neurosteroids in alcohol and substance use. In Neuroactive Steroids in Brain Function, Behavior and Neuropsychiatric Disorders: Novel Strategies for Research and Treatment (pp. 509-538). Springer Netherlands. https://doi.org/10.1007/978-1-4020-6854-6_25

Neurosteroids in alcohol and substance use. / Ginsburg, Brett C; Gerak, Lisa R; McMahon, Lance R.; Roache, John D.

Neuroactive Steroids in Brain Function, Behavior and Neuropsychiatric Disorders: Novel Strategies for Research and Treatment. Springer Netherlands, 2008. p. 509-538.

Research output: Chapter in Book/Report/Conference proceedingChapter

Ginsburg, BC, Gerak, LR, McMahon, LR & Roache, JD 2008, Neurosteroids in alcohol and substance use. in Neuroactive Steroids in Brain Function, Behavior and Neuropsychiatric Disorders: Novel Strategies for Research and Treatment. Springer Netherlands, pp. 509-538. https://doi.org/10.1007/978-1-4020-6854-6_25
Ginsburg BC, Gerak LR, McMahon LR, Roache JD. Neurosteroids in alcohol and substance use. In Neuroactive Steroids in Brain Function, Behavior and Neuropsychiatric Disorders: Novel Strategies for Research and Treatment. Springer Netherlands. 2008. p. 509-538 https://doi.org/10.1007/978-1-4020-6854-6_25
Ginsburg, Brett C ; Gerak, Lisa R ; McMahon, Lance R. ; Roache, John D. / Neurosteroids in alcohol and substance use. Neuroactive Steroids in Brain Function, Behavior and Neuropsychiatric Disorders: Novel Strategies for Research and Treatment. Springer Netherlands, 2008. pp. 509-538
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AB - Allopregnanolone and related neurosteroids share effects with ethanol at several critical targets. Though data are equivocal in humans, acute administration of ethanol (and several other drugs of abuse) increases brain and plasma levels of allopregnanolone in animals. Evidence exists suggesting that this effect of ethanol is mediated via the peripheral or mitochondrial benzodiazepine receptor (PBR). PBR activation can stimulate neurosteroid synthesis and results in anxiolytic effects similar to ethanol, benzodiazepines, and neurosteroids. Further, finasteride, an inhibitor of neurosteroidogenesis, blunts some effects of ethanol in animals and humans. Thus, neurosteroids may modulate or mediate effects of ethanol, benzodiazepines, and barbiturates. Like ethanol and allopregnanolone, benzodiazepines and barbiturates are positive GABA-A receptor modulators. Accordingly, neurosteroids share discriminative stimulus properties with ethanol, benzodiazepines, and barbiturates. Allopregnanolone and related neurosteroids are self-administered by animals, similar to ethanol and other abused drugs. A role for neurosteroids in ethanol tolerance and withdrawal has also emerged, as rodents undergoing ethanol withdrawal are sensitized to neurosteroid effects and alcoholics in withdrawal display reduced allopregnanolone levels. While symmetrical cross tolerance develops between ethanol and benzodiazepines, asymmetrical cross tolerance develops between neurosteroids and benzodiazepines or ethanol, which could be exploited to help treat ethanol, benzodiazepine or barbiturate dependence and withdrawal.

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