Cocaine-associated decision-making: Toward isolating preference.

Ever-increasing evidence suggests that substance use disorder is mediated by decision-making processes, and as such, providing nondrug alternatives can shift maladaptive preferences away from drug reinforcers, such as cocaine. Of note, a recent hypothesis suggests that preference for cocaine is simply a byproduct of cocaine intake, such that the 'direct' effects of cocaine weaken the impact of non-drug alternatives while measuring choice. Conversely, existing quantitative theories of decision-making suggest preference is determined by various dimensions of concurrent reinforcers that in turn determine the relative value of available alternatives. Toward teasing apart the conflicting theories above, we developed a novel drug-choice procedure to control for reinforcer frequency and magnitude (two reinforcer dimensions well known to influence preference) that consequently controls for overall cocaine intake. As predicted by quantitative choice theory, results suggest that cocaine intake and preference are dissociable while measuring choice, with reinforcer frequency and magnitude having independent influence on the relative value of choice alternatives. Furthermore, we demonstrate that the choice procedure is sensitive to various manipulations known to alter cocaine reinforcement, all while keeping cocaine intake constant. Finally, the results point to the process of economic substitution as an important avenue of future neurobehavioral investigation toward the improvement of behavioral and pharmacological therapies for substance use disorders. Overall, the proposed choice procedure will allow for improved isolation of the neurobehavioral processes that mediate drug-associated decision-making in future studies.