Modeling Cannabinoid Withdrawal With Anxiety-Related Behaviors in Long Evans Rats
Cannabinoid withdrawal plays a role in maintaining the use of a drug, thus influencing a substance use disorder (SUD). The symptoms associated with withdrawal in humans, including anxiety and cravings, interfere with efforts to achieve cessation of drug use. I will characterize the behavioral profile of cannabinoid withdrawal in rats using models that measure multiple endophenotypes of cannabinoid dependence that may contribute to withdrawal and craving. Initial studies will be performed using adult male and female Long Evans rats receiving twice daily infusions of the synthetic cannabinoid WIN55,212-2, a full agonist of the CB1 and CB2 receptor, or vehicle via jugular catheter starting at 0.2 mg/kg and increasing to 0.8 mg/kg over 4.5 days. This model produces dependence such that somatic signs of spontaneous withdrawal are observed after 6 hours after the final infusion. Here I used open field, marble burying, and elevated plus maze to measure anxiety related behavior following spontaneous withdrawal for 1 or 2 weeks (between-subjects). The open field test and elevated plus maze are measures of exploratory nature. Marble burying measures repetitive and anxiety like behavior. I expect to see an increase in anxiety-like behaviors in rats treated with WIN55,212-2 and spontaneously withdrawn in comparison to the vehicle group. By solidifying the relationship between anxiety and withdrawal from cannabis, I hope to better understand the influence of these symptoms of withdrawal on craving and relapse.