Abstract
Traditional approaches for evaluating if compounds are reinforcing, and thus a risk for abuse, include preclinical self-administration procedures conducted in the absence of alternative reinforcers. While the track record of this approach for determining abuse potential is good, that for predicting efficacy of addiction treatments is not. An alternate approach would be economic choice between drug and nondrug rewards, with parametrically varied options from trial to trial. This would promote goal-directed decisions between reward modalities and should provide metrics that reflect changes in internal state that influence desirability of a given option. We report herein a high throughput economic choice procedure in which squirrel monkeys choose between a short-lived opiate, remifentanil, and a palatable food reward. Stimuli on touchscreens indicate the amount of each reward type offered by varying the number of reward-specific elements. The rapid clearance of remifentanil avoids accumulation of confounding levels of drug, and permits a large number of trials with a wide range of offers of each reward modality. The use of a single metric encompassing multiple values of each reward type within a session enables estimation of indifference values using logistic regression. This indifference value is sensitive to reward devaluation within each reward domain, and is therefore a useful metric for determining shifts in reward preference, as shown with satiation and pharmacological treatment approaches.
Highlights
Self-administration studies have long served as the cornerstone of preclinical research for understanding drug reinforcement and searching for improved addiction therapies
The Indifference values (IndV) for baseline weeks were stable over the many months of testing as indicated by the lack of a significant correlation between IndV and cumulative dose of remifentanil represented by session number
This report summarizes the establishment of a squirrel monkey model of economic choice between the μ-opioid receptor agonist, remifentanil, and a palatable food alternative
Summary
Self-administration studies have long served as the cornerstone of preclinical research for understanding drug reinforcement and searching for improved addiction therapies. A behavioral approach with real-world parallels is one in which the consumption of drugs comes at the expense of alternative nondrug rewards, given that the choice to use drugs can result in the loss of a job, good family relations, and/or good health [1,2,3]. Cocaine users choose sufficiently high monetary rewards over the option to self-administer cocaine [4], demonstrating that drug users are able to minimize their drug intake when behavioral alternatives are available. Behavioral economic theory and concurrent choice procedures in clinical settings have provided a framework for evaluating how individual variability in severity of addiction relates to distinct factors that could influence subjective valuation as reflected in choice between drug and nondrug rewards. Though addiction severity or treatment success is not being modeled those clinical applications highlight the value of an economic decision-making approach
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