Dynamic Adaptation in Neurosteroid Networks in Response to Alcohol

Deborah (Deb) Finn, Vanessa A. Jimenez

Research output: Chapter in Book/Report/Conference proceedingChapter

2 Citations (Scopus)

Abstract

The term neurosteroid refers to rapid membrane actions of steroid hormones and their derivatives that can modulate physiological functions and behavior via their interactions with ligand-gated ion channels. This chapter will highlight recent advances pertaining to the modulatory effects of a select group of neurosteroids that are primarily potent positive allosteric modulators of γ-aminobutyric acid A receptors (GABA A Rs). Nanomolar concentrations of neurosteroids, which occur in vivo, potentiate phasic and tonic forms of GABA A R-mediated inhibition, indicating that both synaptic and extrasynaptic GABA A Rs possess sensitivity to neurosteroids and contribute to the overall ability of neurosteroids to modulate central nervous system excitability. Common effects of alcohol and neurosteroids at GABA A Rs have stimulated research on the ability of neurosteroids to modulate alcohol’s acute and chronic effects. Background on neurosteroid pharmacology and biosynthetic enzymes will be provided as it relates to experimental findings. Data will be summarized on alcohol and neurosteroid interactions across neuroanatomical regions and models of intoxication, consumption, dependence, and withdrawal. Evidence supports independent regulation of neurosteroid synthesis between periphery and brain as well as across brain regions following acute alcohol administration and during withdrawal. Local mechanisms for fine-tuning neuronal excitability via manipulation of neurosteroid synthesis exert predicted behavioral and electrophysiological responses on GABA A R-mediated inhibition. Collectively, targeting neurosteroidogenesis may be a beneficial treatment strategy for alcohol use disorders.

Original languageEnglish (US)
Title of host publicationHandbook of Experimental Pharmacology
PublisherSpringer New York LLC
Pages55-78
Number of pages24
DOIs
StatePublished - Jan 1 2018

Publication series

NameHandbook of Experimental Pharmacology
Volume248
ISSN (Print)0171-2004
ISSN (Electronic)1865-0325

Fingerprint

Neurotransmitter Agents
Alcohols
gamma-Aminobutyric Acid
GABA-A Receptors
Brain
Steroid hormones
Ligand-Gated Ion Channels
Aminobutyrates
Neurology
Modulators
Central Nervous System
Tuning
Steroids
Hormones
Pharmacology
Derivatives
Membranes
Enzymes
Research

Keywords

  • Allopregnanolone
  • Consumption
  • Ethanol
  • GABA receptors
  • Withdrawal

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Finn, D. D., & Jimenez, V. A. (2018). Dynamic Adaptation in Neurosteroid Networks in Response to Alcohol. In Handbook of Experimental Pharmacology (pp. 55-78). (Handbook of Experimental Pharmacology; Vol. 248). Springer New York LLC. https://doi.org/10.1007/164_2017_82

Dynamic Adaptation in Neurosteroid Networks in Response to Alcohol. / Finn, Deborah (Deb); Jimenez, Vanessa A.

Handbook of Experimental Pharmacology. Springer New York LLC, 2018. p. 55-78 (Handbook of Experimental Pharmacology; Vol. 248).

Research output: Chapter in Book/Report/Conference proceedingChapter

Finn, DD & Jimenez, VA 2018, Dynamic Adaptation in Neurosteroid Networks in Response to Alcohol. in Handbook of Experimental Pharmacology. Handbook of Experimental Pharmacology, vol. 248, Springer New York LLC, pp. 55-78. https://doi.org/10.1007/164_2017_82
Finn DD, Jimenez VA. Dynamic Adaptation in Neurosteroid Networks in Response to Alcohol. In Handbook of Experimental Pharmacology. Springer New York LLC. 2018. p. 55-78. (Handbook of Experimental Pharmacology). https://doi.org/10.1007/164_2017_82
Finn, Deborah (Deb) ; Jimenez, Vanessa A. / Dynamic Adaptation in Neurosteroid Networks in Response to Alcohol. Handbook of Experimental Pharmacology. Springer New York LLC, 2018. pp. 55-78 (Handbook of Experimental Pharmacology).
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