Brain mechanisms mediating the suppression of alcohol-seeking in the face of punishment

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Authors

• LR Halladay
• A Kocharian
• A Holmes

Abstract

Alcohol use disorders (AUDs) are characterized by continued alcohol abuse despite harmful consequences, suggesting that the brain processes that normally serve to regulate punished behaviors are impaired. Prior work has shown that the amygdala is a key brain region encoding the emotional valence of environmental stimuli signifying punishment. Alcohol is known to have strong effects on neurotransmission in the amygdala, but its role in mediating effects of punishment on alcohol-seeking are unknown. To address this, we chronically implanted microelectrodes in the amygdala to record in vivo neuronal activity in mice performing a punished-suppression of alcohol-seeking task. Mice were trained to lever press in order to obtain an alcohol reward. During subsequent probe-tests, they were subjected to mild footshock when the lever was pressed. Neuronal recordings revealed sub-populations of cells in the basolateral and central regions of the amygdala that significantly altered their firing rate either during alcohol consumption or just prior to a punished lever press. Mice that displayed sustained lever pressing during punishment showed a greater degree of neuronal inhibition during punished lever presses, as compared to mice that largely ceased responding during punishment. Retrospective analysis found that in sessions prior to punishment, the ‘punishment-resistant’ mice also displayed a higher number of cells that fired in response to alcohol consumption. Together, these data demonstrate neuronal encoding of punished alcohol-seeking in distinct subregions of the amygdala and suggest that development of resistance to the suppression of alcohol-seeking in the face of harmful consequences may be related to aberrant amygdala function.

Scientific Focus Area: Neuroscience

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