Development of translational preclinical models in substance abuse: Effects of cocaine administration on cocaine choice in humans and non-human primates

• Published in: Pharmacology, biochemistry and behavior Vol. 134; pp. 12 - 21
• Main Authors: Foltin, Richard W., Haney, Margaret, Rubin, Eric, Reed, Stephanie C., Vadhan, Nehal, Balter, Rebecca, Evans, Suzette M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.2015
• Subjects: Adult; Animals; Choice Behavior; Cocaine; Cocaine - administration & dosage; Cocaine-Related Disorders - psychology; Disease Models, Animal; Female; Human; Humans; Macaca mulatta; Macaca mulatta - psychology; Male; Middle Aged; Non-human primate; Placebos; Relapse model; Self Administration; Translational Medical Research; Translational model; Human; Self-administration; Cocaine; Relapse model; Translational model; Non-human primate
• ISSN: 0091-3057; 1873-5177
• DOI: 10.1016/j.pbb.2015.03.023

Human drug use involves repeated choices to take drugs or to engage in alternative behaviors. The purpose of this study was to examine how response cost for cocaine and the value of an alternative reinforcer (opportunity to play a game of chance) and how ‘free’ doses (with minimal response cost) affected cocaine choice. Two laboratory studies of cocaine self-administration were conducted in a group of humans who were habitual cocaine smokers and in a group of rhesus monkeys that intravenously self-administered cocaine. Nine human cocaine smokers who were not seeking treatment for their cocaine were repeatedly presented with the choice to smoke 25mg cocaine base or play a game of chance for a monetary bonus paid at study completion. The response cost for choosing cocaine varied (up to 4000 responses/dose) and the number of game plays varied (up to 8). In this sample of humans, increasing either the response cost for cocaine or increasing the value of the alternative reinforcer did not significantly affect cocaine choice, while increasing both simultaneously slightly decreased cocaine choice and increased choice of the alternative. In monkeys, the dose–response function for cocaine self-administration (10 choices of 0.0125–0.1mg/kg/infusion vs. candy coated chocolate) was steep and we failed to achieve a 50/50 cocaine/candy choice even after substantially manipulating cost and number of candies available. Providing a large ‘free’ self-administered cocaine dose to humans did not significantly affect cocaine choice, whereas in monkeys, a large free dose of cocaine decreased cocaine choice when higher doses of cocaine were available for self-administration. The present results demonstrate that in the laboratory, it is difficult to modify on-going cocaine self-administration behavior in both humans and non-human primates. •Cocaine vs. alternative choice procedures yielded steep cocaine dose–response functions.•Cocaine choice was difficult to disrupt by increasing cocaine cost or value of alternative.•Giving “free” cocaine doses before choice sessions had minimal effects on cocaine choice.