Research Article

A molecular mechanism for choosing alcohol over an alternative reward

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Science  22 Jun 2018:
Vol. 360, Issue 6395, pp. 1321-1326
DOI: 10.1126/science.aao1157

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Finding the vulnerable minority

“Only” about 10 to 15% of people exposed to alcohol develop alcohol-related problems. The behavioral repertoire of people confronted with opportunities to consume alcohol involves numerous choices between this drug reward and healthy alternatives. Augier et al. established a choice procedure that begins to address alcohol addiction in rats (see the Perspective by Spanagel). They found that a minority of outbred rats continued to self-administer alcohol even when a high-value alternative (such as sugar) was available. That minority displayed a remarkable constellation of behavioral traits resembling the human clinical condition, including a high motivation to obtain alcohol and continued use despite adverse consequences. The cause was impaired GABA (γ-aminobutyric acid) clearance in the central amygdala. Postmortem tissue analysis supported the possibility of a similar pathology in human alcoholism.

Science, this issue p. 1321; see also p. 1298

Abstract

Alcohol addiction leads to increased choice of alcohol over healthy rewards. We established an exclusive choice procedure in which ~15% of outbred rats chose alcohol over a high-value reward. These animals displayed addiction-like traits, including high motivation to obtain alcohol and pursuit of this drug despite adverse consequences. Expression of the γ-aminobutyric acid (GABA) transporter GAT-3 was selectively decreased within the amygdala of alcohol-choosing rats, whereas a knockdown of this transcript reversed choice preference of rats that originally chose a sweet solution over alcohol. GAT-3 expression was selectively decreased in the central amygdala of alcohol-dependent people compared to those who died of unrelated causes. Impaired GABA clearance within the amygdala contributes to alcohol addiction, appears to translate between species, and may offer targets for new pharmacotherapies for treating this disorder.

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