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Cellular and Behavioral Interactions of Gabapentin with Alcohol Dependence – Source: Journal of Neuroscience, May 28, 2008

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By Marisa Roberto, et al. • www.ProHealth.com • May 30, 2008


[Note: See “Study supports promise of gabapentin as potential therapy for alcoholism,” for a lay-language report on these important findings from the Scripps Research Institute - which has already initiated controlled trials of gabapentin’s effectiveness as an alcohol (and cannabis) dependence treatment.]

Gabapentin [brand name NeurontinR] is a structural analog of [the neurotransmitter] 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 [alcohol] 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 GABAB receptor antagonist. The sensitivity of the GABA-IPSCs to a GABAB receptor antagonist and an agonist was decreased after chronic ethanol, suggesting that ethanol-induced neuroadaptations of GABAB 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.

Source: Journal of Neuroscience, May 28, 2008. 28(22):5762-5771. By Roberto M, Gilpin NW, O’Dell LE, Cruz MT, Morse AC, Siggins GR, Koob GF. Department of Molecular and Integrative Neurosciences, and Pearson Center for Alcoholism and Addiction Research, The Scripps Research Institute, La Jolla, California; Department of Psychology, University of Texas at El Paso; BrainCells, San Diego, California . [E-mail: mroberto@scripps.edu]





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