Rationale: Stress, a powerful precipitant of drug seeking during abstinence, may also accelerate the return to pathological patterns of intake after initial instances of drug reuse.
Objective: To explore the effect of stress on a learning process underlying relapse, this study assessed the effect of yohimbine on reacquisition of oxycodone seeking.
Methods: One hundred thirty-two male Sprague-Dawley rats underwent place conditioning with oxycodone (2 mg/kg, SC; ×6 days), extinction (vehicle × 6 days), and reconditioning with 0, 0.25, 2, or 5 mg/kg oxycodone (2 days). Yohimbine (0, 2.5, or 5 mg/kg, IP) was administered 30 min prior to reconditioning.
Results: Pretreatment with 2.5 mg/kg yohimbine increased, while 5 mg/kg yohimbine decreased, reacquisition of oxycodone-induced place preference. A follow-up study (n = 30) further indicated that the effect of yohimbine was specific to reacquisition.
Conclusion: The observation that yohimbine can enhance reacquisition of oxycodone seeking supports the hypothesis that stress can facilitate learning processes involved in the unfolding of relapse.