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Cellular and behavioral interactions of gabapentin with alcohol dependence

Academic Article
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Overview

authors

  • Roberto, Marisa
  • Gilpin, N. W.
  • O'Dell, L. E.
  • Cruz, M. T.
  • Morse, A. C.
  • Siggins, George
  • Koob, George

publication date

  • May 2008

journal

  • Journal of Neuroscience  Journal

abstract

  • Gabapentin is a structural analog of GABA that has anticonvulsant properties. Despite the therapeutic efficacy of gabapentin, its molecular and cellular mechanisms of action are unclear. The GABAergic system in the central nucleus of the amygdala (CeA) plays an important role in regulating voluntary ethanol intake. Here, we investigated the effect of gabapentin on GABAergic transmission in CeA slices, on ethanol intake, and on an anxiety measure using animal models of ethanol dependence. Gabapentin increased the amplitudes of evoked GABA receptor-mediated IPSCs (GABA-IPSCs) in CeA neurons from nondependent rats, but decreased their amplitudes in CeA of ethanol-dependent rats. Gabapentin effects were blocked in the presence of a specific GABA(B) receptor antagonist. The sensitivity of the GABA-IPSCs to a GABA(B) receptor antagonist and an agonist was decreased after chronic ethanol, suggesting that ethanol-induced neuroadaptations of GABA(B) receptors associated with ethanol dependence may account for the differential effects of gabapentin after chronic ethanol. Systemic gabapentin reduced ethanol intake in dependent, but not in nondependent, rats and reversed the anxiogenic-like effects of ethanol abstinence using an acute dependence model. Gabapentin infused directly into the CeA also blocked dependence-induced elevation in operant ethanol responding. Collectively, these findings show that gabapentin reverses behavioral measures of ethanol dependence and, in turn, dependence reverses the effects of gabapentin on CeA neurons, and suggest that gabapentin represents a potential medication for treatment of alcoholism.

subject areas

  • Alcoholism
  • Amines
  • Amygdala
  • Animals
  • Behavior, Animal
  • Central Nervous System Depressants
  • Cyclohexanecarboxylic Acids
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Ethanol
  • Excitatory Amino Acid Antagonists
  • GABA Antagonists
  • In Vitro Techniques
  • Inhibitory Postsynaptic Potentials
  • Male
  • Maze Learning
  • Neurons
  • Patch-Clamp Techniques
  • Phosphinic Acids
  • Propanolamines
  • Rats
  • Rats, Wistar
  • Self Administration
  • Synaptic Transmission
  • gamma-Aminobutyric Acid
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Research

keywords

  • IPSC
  • amygdala
  • anxiety
  • ethanol dependence
  • ethanol-self administration
  • paired-pulse facilitation
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Identity

PubMed Central ID

  • PMC2493536

International Standard Serial Number (ISSN)

  • 0270-6474

Digital Object Identifier (DOI)

  • 10.1523/jneurosci.0575-08.2008

PubMed ID

  • 18509038
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Additional Document Info

start page

  • 5762

end page

  • 5771

volume

  • 28

issue

  • 22

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