Fentanyl reinstatement to discriminative cues after conflict in sign- and goal-tracking rats

Martin, D. A.; Keefer, S. E.; Calu, D. J.

doi:10.1101/2022.02.10.479913

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bioRxiv · 10.1101/2022.02.10.479913

Fentanyl reinstatement to discriminative cues after conflict in sign- and goal-tracking rats

Martin, D. A.·Keefer, S. E.·Calu, D. J.

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Abstract

RationaleDiscriminative stimuli (DS) are cues that predict reward availability. DS are resistant to extinction and motivate drug seeking even after long periods of abstinence. Previous studies have demonstrated that sign tracking (ST) and goal tracking (GT) individual differences in Pavlovian approach to food cues predict distinct vulnerabilities to CS and DS reinstatement of cocaine seeking, respectively. Compared to goal-trackers, sign-trackers show heightened CS relapse even after electric barrier induced abstinence. We do not know whether DS relapse persists after electric barrier induced abstinence, or whether tracking-related relapse vulnerabilities generalize to models of opioid relapse. ObjectivesWe sought to determine if DS-induced reinstatement of fentanyl seeking persists in the presence of reduced adverse consequences after electric barrier-induced abstinence. We also aimed to determine whether tracking differences predict the magnitude of DS-induced reinstatement of fentanyl seeking after electric barrier-induced abstinence. MethodsFirst we used Pavlovian lever autoshaping (PLA) training to determine sign-, goal- and intermediate tracking groups in male and female Sprague Dawley rats. We then trained rats in a DS model of intermittent fentanyl self-administration, and extinguished drug seeking by imposing an electric barrier of increasing intensity. We then measured the level of DS-induced reinstatement in the presence of a reduced electric barrier intensity. ResultsWe report that DS produce large increases in fentanyl seeking after electric barrier induced abstinence. Contrary to our expectations, the magnitude of the DS induced reinstatement effect was not related to tracking group. ConclusionsDiscriminative stimuli powerfully motivate opioid seeking, despite continued aversive consequences. Individual differences in Pavlovian approach do not predict the level of DS reinstatement to fentanyl seeking after conflict induced abstinence.

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Martin, D. A., Keefer, S. E., Calu, D. J.. 2022-02-10. Fentanyl reinstatement to discriminative cues after conflict in sign- and goal-tracking rats. https://doi.org/10.1101/2022.02.10.479913

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