Delay discounting as a behavioral phenotype associated with social rank in female and male cynomolgus monkeys: Correlation with kappa opioid receptor availability.

ABSTRACT

Cocaine use disorder (CUD) is a significant problem worldwide, with no FDA-approved treatments. Epidemiological data indicate that only about 17 % of people that use cocaine will meet DSM criteria for CUD. Thus, the identification of biomarkers predictive of eventual cocaine use may be of great value. Two potentially useful predictors of CUD are social hierarchies in nonhuman primates and delay discounting. Both social rank and preference for a smaller, immediate reinforcer relative to a larger, delayed reinforcer have been predictive of CUD. Therefore, we wanted to determine if there was also a relationship between these two predictors of CUD. In the present study, monkeys cocaine-naive responded under a concurrent schedule of 1- vs. 3-food pellets and delivery of the 3-pellet option was delayed. The primary dependent variable was the indifference point (IP), which is the delay that results in 50 % choice for both options. In the initial determination of IP, there were no differences based on sex or social rank of the monkeys. When the delays were redetermined after ~25 baseline sessions (range 5-128 sessions), dominant females and subordinate males showed the largest increases in IP scores from the first determination to the second. Because 13 of these monkeys had prior PET scans of the kappa opioid receptor (KOR), we examined the relationship between KOR availability and IP values and found that the change in IP scores from the first to the second determination significantly negatively predicted average KOR availability in most brain regions. Future studies will examine acquisition to cocaine self-administration in these same monkeys, to determine if IP values are predictive of vulnerability to cocaine reinforcement.