Cocaine choice procedures in animals, humans, and treatment-seekers: Can we bridge the divide?

Abstract

Individuals with cocaine use disorder chronically self-administer cocaine to the detriment of other rewarding activities, a phenomenon best modeled in laboratory drug-choice procedures. These procedures can evaluate the reinforcing effects of drugs versus comparably valuable alternatives under multiple behavioral arrangements and schedules of reinforcement. However, assessing drug-choice in treatment-seeking or abstaining humans poses unique challenges: for ethical reasons, these populations typically cannot receive active drugs during research studies. Researchers have thus needed to rely on alternative approaches that approximate drug-choice behavior or assess more general forms of decision-making, but whether these alternatives have relevance to real-world drug-taking that can inform clinical trials is not well-understood. In this mini-review, we (A) summarize several important modulatory variables that influence cocaine choice in nonhuman animals and non-treatment seeking humans; (B) discuss some of the ethical considerations that could arise if treatment-seekers are enrolled in drug-choice studies; (C) consider the efficacy of alternative procedures, including non-drug-related decision-making and ‘simulated’ drug-choice (a choice is made, but no drug is administered) to approximate drug choice; and (D) suggest opportunities for new translational work to bridge the current divide between preclinical and clinical research.

Evaluation of the “Pipeline” for Development of Medications for Cocaine Use Disorder: A Review of Translational Preclinical, Human Laboratory, and Clinical Trial Research

“…Human laboratory studies were largely conducted after medication approval, likely reflecting regulatory hurdles for studying potential medications for drug use disorders (i.e., the need for drugs to be FDA-approved before administration to humans), as well as the more recent development of laboratory drug self-administration measures in humans (see Moeller and Stoops, 2015). Although these drugs may not have been tested specifically according to our suggested order (e.g., conducting laboratory research in both nonhuman animals and humans before progressing to a clinical trial), the laboratory results demonstrate that self-administration procedures generate outcomes Translational Utility of Laboratory Measures of Cocaine Use consistent with those of clinical trials.…”

“…Although there are many schedules of reinforcement available to measure cocaine self-administration, procedures that require the subject to choose between drug and an alternative reinforcer appear to be the most translational. Choice procedures, which have been adapted for use in animal and human laboratories (Comer et al, 2008;Banks and Negus, 2012;Thomsen et al, 2013;Moeller and Stoops, 2015), reflect a critical aspect of the disorder in that drug abusers choose to allocate their time and resources toward procuring and using drugs and away from other commodities and activities that could serve as reinforcers. A greater effort to test potential medications using similar methods across laboratories will help to clarify whether results in preclinical and clinical settings support the same conclusions.…”

Abstinence reverses EEG-indexed attention bias between drug-related and pleasant stimuli in cocaine-addicted individuals

“…43 This interview determined that individuals with CUD met the criteria for current cocaine dependence or cocaine dependence in partial or sustained remission.…”

“…16,39,40 Hereafter, these differential scores are referred to as pleasant (i.e., pleasant -neutral) and drug (i.e., drug -neutral) LPP scores. Moreover, differential scores for the drug pictures relative to the pleasant pictures were also created, as done previously 18,30 as a parameter of attention bias to 2 salient reinforcers; a similar contrast, evaluating drugtaking behaviour in the presence of another concurrently available salient nondrug alternative, is used in drug choice procedures across species [41][42][43] and mirrors the addiction diagnostic criterion of using the drug of choice to the exclusion of other activities. 44 …”

Medications for substance use disorders (SUD): emerging approaches

“…This may occur for a variety of practical, ethical and regulatory reasons [199]. It is unclear if the study of such “non-treatment seeking” participants results in challenges to appropriate “go/no-go” decisions for progression to further clinical development [18,199]. It is possible that the practice of studying non-treatment seekers may affect development of different types of pharmacotherapies in a different manner.…”