Monkey Models of Polysubstance Misuse: Reinforcing Effects of Cocaine With and Without Alcohol or Nicotine Co-Use

Abstract ID 100775 Poster Board 113 Cocaine use disorder (CUD) continues to be a public health crisis, with no FDA-approved treatments. Estimates indicate that <80% of people who use cocaine co-use nicotine and nearly 90% of people with CUD co-use alcohol. The present set of studies extended animal research on cocaine misuse to include the co-use of nicotine and/or alcohol in female and male monkeys. In Experiment 1, male rhesus monkeys (N = 3) self-administered cocaine (0.001-0.1 mg/kg/injection) alone and with nicotine (0.01-0.03 mg/kg/injection) under a progressive-ratio schedule of reinforcement. When nicotine was added to cocaine, there was a significant leftward shift and a significant increase in the peak number of injections. In Experiment 2, socially housed female and male cynomolgus monkeys (N = 14) self-administered cocaine under a concurrent drug-vs-food choice schedule. Combining nicotine significantly shifted the cocaine dose-response curve to the left in females but not in males, with no evidence of social rank differences. To assess nicotine9s effects on the reinforcing strength of cocaine, delays were added to the presentation of drug; the co-use of nicotine and cocaine required significantly longer delays to decrease drug choice, compared with cocaine alone. Experiment 3 examined the impact of alcohol use on cocaine self-administration. When alcohol and cocaine are co-used, there is an active metabolite formed, cocaethylene. Using a progressive-ratio schedule of reinforcement, we recently showed that intravenous cocaethylene had reinforcing effects that were similar in potency and reinforcing strength to cocaine. In the present study, the reinforcing strength of cocaethylene was compared to cocaine using a concurrent schedule of reinforcement with food as the alternative to drug. Although the potency of cocaethylene and cocaine were similar under the concurrent schedule, we hypothesized that behavioral interventions, such as using delay discounting, would show that the reinforcing strength of cocaethylene was greater than that of cocaine. Preliminary findings indicate that longer delays were necessary to decrease cocaethylene preference compared with those needed to decrease cocaine preference. Overall, the results from the nicotine + cocaine studies and the preliminary findings with cocaethylene suggest that animal models of CUD only examining cocaine self-administration may underestimate the efficacy of an intervention, perhaps providing false positive outcomes. Results from studies using co-use of other substances with cocaine will aid in the development of personalized medicine strategies for cocaine use disorder that incorporates the co-use of alcohol and/or nicotine-related products. Supported by NIDA grants DA017763-15 and DA041349-06.