Reinforcer pathology in cocaine use disorder: Temporal window determines cocaine valuation.

Abstract

The Experimental Medicine Approach offers a unique perspective to determine clinical behavior change by engaging a target underlying the cause of a disorder. The present work engaged a novel target of addiction, Reinforcer Pathology, in two studies to test changes in behavior among individuals with cocaine use disorder. In Study 1, n = 44 participants engaged the temporal window with episodic future thinking (EFT), a positive prospection exercise. Changes in temporal view and cocaine valuation were tested using delay discounting and behavioral economic demand, respectively. Additionally, a computational model assessed the relative reliance on the near- and far-sighted systems during EFT. In Study 2, n = 71 engaged the temporal window with a negatively-valenced hurricane scenario to test the opposite effects on window length and cocaine valuation. Results demonstrated systematic and symmetrical engagement of the behavioral target. Study 1 robustly replicated previous work, wherein EFT lengthened the temporal window and decreased cocaine valuation. Moreover, EFT increased the weighting of the modeled far-sighted system, increasing the relative impact of long-term discounting decisions. Study 2 produced opposite outcomes, shortened temporal window and increased cocaine valuation. This approximately equal and opposite reaction to the manipulations supports reinforcer pathology theory and implicates the temporal window over which rewards are valued as a target to be pushed and pulled to produce clinically meaningful behavior change. Using the Experimental Medicine Approach as a guide, future work should identify new potential interventions to engage reinforcer pathology and use the clinically relevant outcomes as a litmus test for mechanism.