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

View ORCID ProfileDavid A. Martin, View ORCID ProfileSara E. Keefer, View ORCID ProfileDonna J. Calu
doi: https://doi.org/10.1101/2022.02.10.479913
David A. Martin
Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USA
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Sara E. Keefer
Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USA
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Donna J. Calu
Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USA
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  • For correspondence: dcalu@som.umaryland.edu
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Abstract

Rationale Discriminative 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.

Objectives We 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.

Methods First 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.

Results We 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.

Conclusions Discriminative 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.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted February 10, 2022.
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Fentanyl reinstatement to discriminative cues after conflict in sign- and goal-tracking rats
David A. Martin, Sara E. Keefer, Donna J. Calu
bioRxiv 2022.02.10.479913; doi: https://doi.org/10.1101/2022.02.10.479913
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Fentanyl reinstatement to discriminative cues after conflict in sign- and goal-tracking rats
David A. Martin, Sara E. Keefer, Donna J. Calu
bioRxiv 2022.02.10.479913; doi: https://doi.org/10.1101/2022.02.10.479913

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