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The effects of voluntary THC consumption on oxycodone demand and oxycodone seeking in a novel rat model

Katherine Driver
University of Florida

Co-Authors: Cassidy Jones-Goucher1, Alexandra Sanchez1, Barry Setlow1, Marek Schwendt1, Lori Knackstedt1
1University of Florida

Opioid use disorder (OUD) lacks an effective, broad-spectrum treatment. Limited clinical evidence suggests that co-use of cannabinoids can reduce the rates of opioid dependence and severity of withdrawal, though at the cost of elevated anxiety, and depression. Despite poor understanding of risks and benefits of opioid-cannabinoid interactions, OUD is currently considered a qualifying condition for the use of medical marijuana in several US states. Thus, well-controlled, translational animal models are necessary to investigate the neural and behavioral consequences of cannabinoid-opioid co-use. The current study aimed to investigate the effects of daily oral D9- tetrahydrocannabinol (THC) consumption on behavioral economic demand for intravenously self-administered (IVSA) oxycodone in male and female Sprague-Dawley rats. Rats were first trained to self-administer oxycodone or sucrose. Rats administering oxycodone were trained under a FR (fixed ratio) 1 and 3 schedule for 6 days each. Rats administering sucrose trained at FR 1 for the duration of the experiment. Somatic signs of withdrawal and anxiety-like behavior were assessed at 22 hr withdrawal. After reaching stable oxycodone intake during training, rats underwent demand curve procedures in which FR requirements to earn a single oxycodone infusion increased in quarter log unit increments until zero infusions were attained for a given FR. Throughout the demand curve, rats also received access to unsweetened gelatin containing either THC or Vehicle in the home cage for one hour following the oxycodone/sucrose session. Oxycodone self-administration was re-established on an FR-3 schedule prior to 14 days of home cage abstinence. On Day 15, rats underwent a cued relapse test. No effects of sex on oxycodone seeking behavior or intake were found during the training portion of either self-administration period (sucrose or oxycodone). THC consumption increases demand elasticity for oxycodone IVSA in male and female rats, with no effects on sucrose intake. The findings of this study, once completed, will provide first-ever preclinical evidence regarding the effects of THC on motivation to seek oxycodone.

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