Use of Preclinical Drug Vs. Food Choice Procedures to Evaluate Candidate Medications for Cocaine Addiction

Abstract

Opinion Statement Drug addiction is a disease that manifests as an inappropriate allocation of behavior towards the procurement and use of the abused substance and away from other behaviors that produce more adaptive reinforcers (e.g. exercise, work, family and social relationships). The goal of treating drug addiction is not only to decrease drug-maintained behaviors, but also to promote a reallocation of behavior towards alternative, nondrug reinforcers. Experimental procedures that offer concurrent access to both a drug reinforcer and an alternative, nondrug reinforcer provide a research tool for assessment of medication effects on drug choice and behavioral allocation. Choice procedures are currently the standard in human laboratory research on medications development. Preclinical choice procedures have been utilized in biomedical research since the early 1940’s, and during the last 10–15 years, their use for evaluation of medications to treat drug addiction has increased. We propose here that parallel use of choice procedures in preclinical and clinical studies will facilitate translational research on development of medications to treat cocaine addiction. In support of this proposition, a review of the literature suggests strong concordance between preclinical effectiveness of candidate medications to modify cocaine choice in nonhuman primates and rodents and clinical effectiveness of these medications to modify either cocaine choice in human laboratory studies or metrics of cocaine abuse in patients with cocaine use disorder. The strongest evidence for medication effectiveness in preclinical choice studies has been obtained with maintenance on the monoamine releaser d-amphetamine, a candidate agonist medication for cocaine use analogous to use of methadone to treat heroin abuse or nicotine formulations to treat tobacco dependence.

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

“…We conducted a clinical diagnostic interview with all participants at baseline, consisting of the Structured Clinical Interview for DSM-IV axis I disorders; 38,39 the Addiction Severity Index, 40 a semistructured interview instrument that assesses the severity as well as recent and lifetime history of alcohol-and drugrelated problems as they relate to 7 problem areas (medical, employment, legal, alcohol, other drug use, family-social functioning and psychological status); the 18-item Cocaine Selective Severity Assessment Scale, 41 designed to evaluate cocaine abstinence/withdrawal signs and symptoms (i.e., sleep impairment, anxiety, energy levels, craving, and depressive symptoms) within 24 hours of the interview; the 5-item Severity of Dependence Scale; 42 and the 5-item Cocaine Craving Questionnaire. 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 …”

Development of a translational model to screen medications for cocaine use disorder I: Choice between cocaine and food in rhesus monkeys

“…A change in species is unavoidable at this transition; however, the fidelity of translation may benefit from (1) the use of nonhuman primates as animal subjects due to their high biological similarity with humans, especially with regard to monoaminergic systems affected by cocaine and many candidate medications (Weerts et al, 2007; Bradberry, 2008), and (2) the use of homologous experimental procedures that minimize discrepancies in variables other than species and maximize potential for direct comparison of results across species (Czoty et al, 2016b; Foltin et al, 2015; Yu, 2011). In particular, recent reviews on medications development for drug abuse research have suggested that translation is optimized by use of procedures that test effects of medication maintenance on choice between the abused drug and an alternative non-drug reinforcer (Haney and Spealman, 2008; Jones and Comer, 2013; Banks et al, 2015a; Czoty et al, 2016b). Although choice procedures have been developed for use in both animals and humans, there remain discrepancies in many procedural details for the most commonly used approaches (Banks et al, 2012; Jones and Comer, 2013).…”

“…Lisdexamfetamine is an amphetamine prodrug approved for treatment of ADHD and compulsive eating disorder (Blick and Keating, 2007; Hutson et al, 2014), and it was selected for initial testing because preclinical and clinical research suggests that it might also be useful for treating cocaine use disorder (Banks et al, 2015; Mooney et al, 2015). Furthermore, maintenance on its metabolite, d-amphetamine, has been shown to decrease cocaine self-administration across a broad range of experimental conditions in rats, rhesus monkeys, human-laboratory studies, and placebo-controlled, double-blind clinical trials (Herin et al, 2010; Negus and Henningfield, 2015; Nuijten et al, 2016).…”

Effects of 7-day repeated treatment with the 5-HT2A inverse agonist/antagonist pimavanserin on methamphetamine vs. food choice in male rhesus monkeys

“…First, preclinical drug vs. food choice procedures have been predictive of human drug abuse and addiction (Ahmed, 2010; Banks and Negus, 2012). Second, preclinical drug vs. food choice procedures provide a dependent measure of behavioral allocation that may be less sensitive to reinforcement-independent rate-altering drug effects produced by treatment drugs that may have potential as candidate medications (Banks et al, 2015). Pimavanserin was selected because it is more selective for 5-HT 2A vs. 5-HT 2C receptors than M100,907 (Vanover et al, 2006) and has been recently approved by the Food and Drug Administration for Parkinson’s disease-induced psychosis treatment (Cummings et al, 2014; Walsh, 2016).…”