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Anti-relapse neurons in the infralimbic cortex of rats drive relapse-suppression by drug omission cues

Amanda Laque,Genna L De Ness,Grant E. Wagner,Hermina Nedelescu,Ayla Carroll,D. Watry,Tony M Kerr,E. Koya,B. Hope,F. Weiss,G. Elmer,N. Suto

Published 2019 in Nature Communications

ABSTRACT

Drug addiction is a chronic relapsing disorder of compulsive drug use. Studies of the neurobehavioral factors that promote drug relapse have yet to produce an effective treatment. Here we take a different approach and examine the factors that suppress—rather than promote—relapse. Adapting Pavlovian procedures to suppress operant drug response, we determined the anti-relapse action of environmental cues that signal drug omission (unavailability) in rats. Under laboratory conditions linked to compulsive drug use and heightened relapse risk, drug omission cues suppressed three major modes of relapse-promotion (drug-predictive cues, stress, and drug exposure) for cocaine and alcohol. This relapse-suppression is, in part, driven by omission cue-reactive neurons, which constitute small subsets of glutamatergic and GABAergic cells, in the infralimbic cortex. Future studies of such neural activity-based cellular units (neuronal ensembles/memory engram cells) for relapse-suppression can be used to identify alternate targets for addiction medicine through functional characterization of anti-relapse mechanisms. Drug addiction is a chronic disorder and many sufferers experience relapses even after a period of successful abstinence. Here, the authors reveal a subset of neurons in the rat infralimbic cortex that suppresses relapse into cocaine or alcohol use by responding to drug-omission cues.

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