Maladaptive cue-controlled cocaine-seeking habits promote increased relapse severity in rats.

Fouyssac, M.; Pena-Oliver, Y.; Puaud, M.; Lim, N.; Giuliano, C.; Everitt, B. J.; Belin, D.

doi:10.1101/2021.02.01.429216

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bioRxiv · 10.1101/2021.02.01.429216

Maladaptive cue-controlled cocaine-seeking habits promote increased relapse severity in rats.

Fouyssac, M.·Pena-Oliver, Y.·Puaud, M.·Lim, N.·Giuliano, C.·Everitt, B. J.·Belin, D.

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Abstract

The inflexible pursuit of drug-seeking and great tendency to relapse that characterize addiction has been associated with the recruitment of the dorsolateral striatum-dependent habit system. However, the mechanisms by which maladaptive drug-seeking habits influence subsequent relapse are obscure. Here, we show that rats with a long history of cocaine-seeking, controlled by drug-paired cues and mediated by the habit system, show highly exacerbated drug-seeking at relapse that is not mediated by cocaine withdrawal. This heightened tendency to relapse is underpinned by transient engagement of the dorsomedial striatum goal-directed system and reflects emergent negative urgency resulting from the prevention of enacting the seeking habit during abstinence. These results reveal a novel mechanism underlying the pressure to relapse and indicate a target for preventing it. One Sentence SummaryInstrumental deprivation triggers flexibility in the well-established cue-controlled cocaine-seeking behaviour.

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Fouyssac, M., Pena-Oliver, Y., Puaud, M., Lim, N., Giuliano, C., Everitt, B. J., Belin, D.. 2021-02-02. Maladaptive cue-controlled cocaine-seeking habits promote increased relapse severity in rats.. https://doi.org/10.1101/2021.02.01.429216

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