Insights from Preclinical Choice Models on Treating Drug Addiction

Abstract

Substance-use disorders are a global public health problem that arises from behavioral misallocation between drug use and more adaptive behaviors maintained by nondrug alternatives (e.g., food or money). Preclinical drug self-administration procedures that incorporate a concurrently available nondrug reinforcer (e.g., food) provide translationally relevant and distinct dependent measures of behavioral allocation (i.e., to assess the relative reinforcing efficacy of the drug) and behavioral rate (i.e., to assess motor competence). In particular, preclinical drug versus food 'choice' procedures have produced increasingly concordant results with both human laboratory drug self-administration studies and double-blind placebo-controlled clinical trials. Accordingly, here we provide a heuristic framework of substance-use disorders based on a behavioral-centric perspective and recent insights from these preclinical choice procedures. Keywordschoice; addiction; preclinical model; drug self-administration; substance-use disorder Trends Substance-use disorders (i.e., drug addiction) are increasingly being conceptualized as disorders of behavioral misallocation between drug and nondrug reinforcers.Preclinical drug versus food choice procedures are increasingly being utilized to elucidate environmental, pharmacological, and biological mechanisms associated with this behavioral misallocation.Preclinical drug versus food choice procedures provide distinct dependent measures that dissociate drug reinforcement (i.e., allocation of behavior) from motor competence (i.e., rate of behavior). Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. HHS Public Access Author Manuscript Author ManuscriptAuthor Manuscript Author ManuscriptAlternative nondrug reinforcer availability and temporal delivery impact behavioral allocation.Preclinical drug versus food choice procedures are being developed for abused drugs other than cocaine.Biological variables are an emerging as important determinants of behavioral allocation between drug and nondrug reinforcers. Drug AddictionDrug addiction is an insidious and global public health problem. . Furthermore, six of the 11 diagnostic criteria used for substance-use disorders are based on the allocation of behavior towards the procurement and use of the substance compared with other behaviors maintained by nondrug and presumably more adaptive alternative reinforcers (e.g., food, money, or social commendation). Thus, the diagnosis of substance-use disorders takes a behavioral-centric perspective and implies that such disorders arise from behavioral misallocat...

Maintenance on naltrexone + amphetamine decreases cocaine-vs.-food choice in male rhesus monkeys

“…There was also a trend for naltrexone to enhance the cocaine choice-decreasing effects of the higher dose of 0.1 mg/kg/h amphetamine, but this effect did not achieve criteria for statistical significance. Insofar as treatment-induced decreases in cocaine vs. food choice are predictive of therapeutic efficacy to reduce cocaine use clinically (Banks and Negus, 2017; Czoty et al, 2016), these results suggest that addition of naltrexone may increase potency of amphetamine as a maintenance medication for cocaine use disorder.…”

“…Under these conditions, morphine generally decreased rates of cocaine self-administration, consistent with the morphine-induced decrease in overall reinforcement rate observed here. Choice procedures are distinguished from these other types of procedures by their evaluation of behavioral allocation as well as behavioral rate, and choice measures of behavioral allocation provide a relatively rate-independent measure of drug reinforcement (Banks and Negus, 2012, 2017). In the present study, morphine maintenance both increased cocaine vs. food choice and decreased overall rates of reinforcement, suggesting that mu receptor activation both increases the relative reinforcing effects of cocaine in comparison to food while also decreasing overall motor competence to engage in operant responding.…”

“…The choice procedure was chosen for three primary reasons (Banks and Negus, 2012, 2017; Czoty et al, 2016; Heyman, 2009; Jones and Comer, 2013). First, drug choice procedures provide a dependent measure of drug reinforcement (i.e., percent drug choice) that is relatively independent of treatment effects on overall rates of responding or reinforcement.…”

Effects of Acute and Chronic Treatments with Dopamine D2 and D3 Receptor Ligands on Cocaine versus Food Choice in Rats

“…Furthermore, effects on cocaine selfadministration (i.e., direct reinforcing effects of cocaine) have predicted clinical efficacy better than modulation of subjective or conditioned effects alone (Comer et al, 2008;Haney and Spealman, 2008). One type of self-administration assay, choice procedures, is gaining popularity, with various proposed advantages over single-reinforcer assays (Banks et al, 2015a;Banks and Negus, 2017). Choice procedures allow behavior allocation to be assessed independently of rates of responding, and they also allow simultaneous evaluation of effects on cocaine and food intake.…”

Lorcaserin maintenance fails to attenuate heroin vs. food choice in rhesus monkeys

“…Drug-vs.-food choice procedures provide an alternative strategy to dissociate selective treatment effects on opioid reinforcement (evaluated as changes in behavioral Lorcaserin Effects on Heroin Choice 5 allocation between drug and food choice) from non-selective treatment effects on operant responding (evaluated as changes in overall behavioral rates maintained by either drug or food choice) (Griffiths et al, 1976;Hart et al, 2000;Johanson, 1975;Negus, 2006;Woolverton and Balster, 1981). Second, these procedures have increasingly demonstrated translational concordance with both human laboratory studies and clinical trials across a broad range of abused drug classes, including opioids (for review, see (Banks, 2017;Banks and Negus, 2017b;Negus and Banks, 2013)). To provide a framework for interpreting lorcaserin effects, the effects of two other manipulations were examined.…”