Koob GF. A role for GABA mechanisms in the motivational effects of alcohol. Biochem Pharmacol 68: 1515-1525

Department of Neuropharmacology, The Scripps Research Institute, 1055 North Pines Road, La Jolla, CA 92037, USA.
Biochemical Pharmacology (Impact Factor: 5.01). 11/2004; 68(8):1515-25. DOI: 10.1016/j.bcp.2004.07.031
Source: PubMed


Low doses of ethanol have been hypothesized to act directly via proteins that form ligand-gated receptor channels, such as the gamma-aminobutyric acid (GABA) receptor complex, to allosterically alter function, particularly in specific brain areas such as those hypothesized to be involved in ethanol reinforcement. At the pharmacological level, one can antagonize the effects of ethanol with GABA antagonists, particularly its sedative, anxiolytic-like and acute reinforcing actions. Brain sites involved in the GABAergic component of ethanol reinforcement include the ventral tegmental area, elements of the extended amygdala (including the central nucleus of the amygdala), and the globus pallidus. Chronic administration of ethanol sufficient to produce dependence and increased ethanol intake are associated with increased GABA release in the amygdala and increased sensitivity to GABA agonists. A hypothesis is proposed that GABAergic interactions with the brain stress neurotransmitter corticotropin-releasing factor in specific elements of the extended amygdala may be an important component for the motivation for excessive drinking associated with the transition from social drinking to addiction.

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    • "Third, GABA receptor genes confer increased risk for substance use disorders through disinhibition coupled with heightened response to environmental cues (Beuten et al. 2005; Enoch 2008; Grucza and Bierut 2005; Koob 2004). The GABA system plays a major role in impulsivity and increased craving in response to stress (Dai et al. 2009; Enoch et al. 2006; Villafuerte et al. 2012). "

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    • "GABAARs mediate several important effects of alcohol. Considerable evidence indicates that GABAARs are the major target of EtOH in the CNS28,29,30,31,32. Some studies show that short-term alcohol exposure increases the inhibitory effect of GABAARs; however, many factors determine whether GABAARs respond to short-term alcohol exposure33. "
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    • "It can for example, act on the GABA-releasing (i.e., presynaptic) neuron, causing an increase in GABA release; or it can act on the signal-receiving (i.e., postsynaptic) neuron facilitating the activity of the GABAA receptor. The consumption of alcohol is suppressed by compounds that interfere with the actions of the GABAA receptor (i.e., GABAA receptor antagonists) as well as compounds that stimulate the GABAB receptor (i.e., GABAB agonists) in the nucleus accumbens, ventral pallidum, bed nucleus of the stria terminalis and amygdala.[15] "
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