Investigating discriminative stimulus modulation of opioid seeking after conflict-induced abstinence in sign- and goal-tracking rats

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) differences in Pavlovian approach predict distinct cue-modulated vulnerabilities to cocaine reinstatement. GT rats show heightened reinstatement to contextual and DS, while ST rats show heightened reinstatement to discrete stimuli. Here we examine whether DS modulate reinstatement after electric barrier-induced abstinence and whether tracking-related relapse vulnerabilities generalize to opioid relapse.

Objectives: We examine whether DS-modulated reinstatement to fentanyl seeking persists in the presence of reduced adverse consequences after electric barrier-induced abstinence. We also examine whether tracking differences predict the magnitude of DS-modulated reinstatement of fentanyl seeking after electric barrier-induced abstinence.

Methods: 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-modulated reinstatement in the presence of a reduced electric barrier intensity.

Results: We report that DS strongly modulate fentanyl seeking after electric barrier-induced abstinence. DS-modulation of fentanyl acquisition, electric barrier-induced abstinence, and reinstatement was similar for sign- and goal-tracking groups.

Conclusions: Discriminative stimuli powerfully motivate opioid seeking, despite continued aversive consequences. Pavlovian approach differences do not predict the level of DS-modulated reinstatement to fentanyl seeking after conflict-induced abstinence.