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A molecular mechanism for choosing alcohol over an alternative reward.

Science. 2018 Jun 22;360(6395):1321-1326
Eric Augier 1 , Estelle Barbier 2 , Russell S Dulman 3 , Valentina Licheri 4 , Gaëlle Augier 2 , Esi Domi 2 , Riccardo Barchiesi 2 , Sean Farris 5 , Daniel Nätt 2 , R Dayne Mayfield 5 , Louise Adermark 4 , Markus Heilig 2
Eric Augier 1 , Estelle Barbier 2 , Russell S Dulman 3 , Valentina Licheri 4 , Gaëlle Augier 2 , Esi Domi 2 , Riccardo Barchiesi 2 , Sean Farris 5 , Daniel Nätt 2 , R Dayne Mayfield 5 , Louise Adermark 4 , Markus Heilig 2
+ et al

[No authors listed]

Author information
  • 1 Center for Social and Affective Neuroscience, IKE, Linköping University, Linköping, 581 83, Sweden. eric.augier@liu.se.
  • 2 Center for Social and Affective Neuroscience, IKE, Linköping University, Linköping, 581 83, Sweden.
  • 3 Center for Alcohol Research in Epigenetics, Department of Psychiatry, University of Illinois, Chicago, IL 60612, USA.
  • 4 Department of Psychiatry and Neurochemistry, Sahlgrenska Academy, University of Göteborg, 413 90 Göteborg, Sweden.
  • 5 The Waggoner Center for Alcohol and Addiction Research, University of Texas, Austin, TX 78712, USA.

摘要


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.