Pharmacological Validation of a Translational Model of Cocaine Use Disorder: Effects of d-Amphetamine Maintenance on Choice Between Intravenous Cocaine and a Nondrug Alternative in Humans and Rhesus Monkeys

• Published in: Experimental and clinical psychopharmacology Vol. 28; no. 2; pp. 169 - 180
• Main Authors: Lile, Joshua A., Johnson, Amy R., Banks, Matthew L., Hatton, Kevin W., Hays, Lon R., Nicholson, Katherine L., Poklis, Justin L., Rayapati, Abner O., Rush, Craig R., Stoops, William W., Negus, S. Stevens
• Format: Journal Article
• Language: English
• Published: United States American Psychological Association 01-04-2020
• Subjects: Administration, Intravenous; Adolescent; Adult; Animal; Animals; Blood Plasma; Choice Behavior; Choice Behavior - drug effects; Cocaine; Cocaine - administration & dosage; Cocaine-Related Disorders - drug therapy; Concurrent Reinforcement Schedules; Dextroamphetamine; Dextroamphetamine - pharmacology; Dextroamphetamine - therapeutic use; Drug Self Administration; Female; Human; Humans; Macaca mulatta; Male; Middle Aged; Monkeys; Self Administration; Substance Use Disorder; Young Adult; subjective effects; nonhuman primates; plasma; reinforcing effects; progressive-ratio
• ISSN: 1064-1297; 1936-2293
• DOI: 10.1037/pha0000302

Drug self-administration procedures are the gold standard for laboratory research to study mechanisms of drug use disorders and evaluate candidate medications. However, preclinical-to-clinical translation has been hampered by a lack of coordination. To address this limitation, we previously developed homologous intravenous (IV) cocaine choice self-administration procedures in rhesus monkeys and humans, and then demonstrated their functional equivalence. The present studies sought to determine the sensitivity of these procedures to d-amphetamine maintenance. Three (N = 3) rhesus monkeys with histories of cocaine self-administration and 16 (N = 16) humans with cocaine use disorder completed the studies. Monkeys were maintained on IV d-amphetamine (0, 0.019, 0.037 and 0.074 mg/kg/h), and then completed 7 sessions during each condition in which they completed 9 choice trials to receive 0.14 mg/kg/injection IV cocaine (corresponding to 10 mg/70 kg in humans) or 10 food pellets under independent, concurrent progressive-ratio schedules. Humans were maintained on oral extended release d-amphetamine (0, 30 and 60 mg/day, corresponding to the lowest 3 doses in monkeys) and participated in 12 sessions in which they chose money ($6.00) or IV cocaine (0, 3, 10 and 30 mg/70 kg). Blood samples were taken to compare d-amphetamine plasma levels across species. In monkeys and humans, d-amphetamine reduced the number of cocaine choices and produced comparable blood levels at equivalent daily doses. d-Amphetamine had similar efficacy, though lower potency, at reducing choice for an equivalent cocaine dose in monkeys relative to humans. These coordinated studies support the utility of these procedures as a translational model for cocaine use disorder.
Public Health Significance
The present studies demonstrated that the use of coordinated procedures in monkeys and humans yielded similar decreases in cocaine choice during d-amphetamine maintenance across species. The concordance of these results, and with clinical trials that found reductions in cocaine use in patients treated with d-amphetamine, supports the utility of these procedures as a translational laboratory model of cocaine use disorder.