A molecular mechanism for choosing alcohol over an alternative reward

作者：Augier Eric^*; Barbier Estelle; Dulman Russell S; Licheri Valentina; Augier Gaelle; Domi Esi; Barchiesi Riccardo; Farris Sean; Natt Daniel; Mayfield R Dayne; Adermark Louise; Heilig Markus

来源：Science, 2018, 360(6395): 1321-+.

DOI：10.1126/science.aao1157

Alcohol addiction leads to increased choice of alcohol over healthy rewards. We established an exclusive choice procedure in which similar to 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 g-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.

• 出版日期2018-6-22