A cortical-brainstem circuit predicts and governs compulsive alcohol drinking

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Science  22 Nov 2019:
Vol. 366, Issue 6468, pp. 1008-1012
DOI: 10.1126/science.aay1186

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A brain circuit to control alcohol intake

Most people are exposed to alcohol at some point in their lives, but only a small fraction will develop a compulsive drinking disorder. Siciliano et al. first established a behavioral measure to assess how predisposition interacts with experience to produce compulsive drinking in a subset of mice (see the Perspective by Nixon and Mangieri). In search of the underlying neurobiological mechanism, they discovered that a discrete circuit between the medial prefrontal cortex and brainstem is central for the development of compulsive drinking. This circuit serves as both a biomarker for the development of compulsive drinking and a driver of its expression. It can bidirectionally control compulsive behavior by mitigating or mimicking punishment signals.

Science, this issue p. 1008; see also p. 947


What individual differences in neural activity predict the future escalation of alcohol drinking from casual to compulsive? The neurobiological mechanisms that gate the transition from moderate to compulsive drinking remain poorly understood. We longitudinally tracked the development of compulsive drinking across a binge-drinking experience in male mice. Binge drinking unmasked individual differences, revealing latent traits in alcohol consumption and compulsive drinking despite equal prior exposure to alcohol. Distinct neural activity signatures of cortical neurons projecting to the brainstem before binge drinking predicted the ultimate emergence of compulsivity. Mimicry of activity patterns that predicted drinking phenotypes was sufficient to bidirectionally modulate drinking. Our results provide a mechanistic explanation for individual variance in vulnerability to compulsive alcohol drinking.

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