Development of translational preclinical models in substance abuse: Effects of cocaine administration on cocaine choice in humans and non-human primates.
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.
Division on Substance Abuse, New York State Psychiatric Institute and Department of Psychiatry, Columbia University Medical Center, 1051 Riverside Drive, Unit 120, New York, NY 10032, USA. Electronic address: rwf2@cumc.columbia.edu.
Richard W
RW
Foltin
Division on Substance Abuse, New York State Psychiatric Institute and Department of Psychiatry, Columbia University Medical Center, 1051 Riverside Drive, Unit 120, New York, NY 10032, USA.
Margaret
M
Haney
Department of Psychiatry, Harlem Hospital, 506 Lenox Ave., New York, NY 10037, USA.
Eric
E
Rubin
Division on Substance Abuse, New York State Psychiatric Institute and Department of Psychiatry, Columbia University Medical Center, 1051 Riverside Drive, Unit 120, New York, NY 10032, USA.
Stephanie C
SC
Reed
Department of Psychiatry, Stony Brook University School of Medicine, Health Sciences Tower 10-040K, Stony Brook, NY 11794, USA.
Nehal
N
Vadhan
Division on Substance Abuse, New York State Psychiatric Institute and Department of Psychiatry, Columbia University Medical Center, 1051 Riverside Drive, Unit 120, New York, NY 10032, USA.
Rebecca
R
Balter
Division on Substance Abuse, New York State Psychiatric Institute and Department of Psychiatry, Columbia University Medical Center, 1051 Riverside Drive, Unit 120, New York, NY 10032, USA.
Suzette M
SM
Evans
D000328:Adult; D000818:Animals; D002755:Choice Behavior; D003042:Cocaine / Q000008:administration & dosage*; D019970:Cocaine-Related Disorders / Q000523:psychology*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008253:Macaca mulatta / Q000523:psychology*; D008297:Male; D008875:Middle Aged; D010919:Placebos; D012646:Self Administration; D057170:Translational Research, Biomedical
D010919:Placebos; D003042:Cocaine
Cocaine; Human; Non-human primate; Relapse model; Self-administration; Translational model