Maladaptive cue-controlled cocaine-seeking habits promote increased relapse severity in rats
biorxiv(2021)
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 Summary Instrumental deprivation triggers flexibility in the well-established cue-controlled cocaine-seeking behaviour.
### Competing Interest Statement
The authors have declared no competing interest.
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Key words
relapse severity,habits,cue-controlled,cocaine-seeking
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