Development of a translational model to screen medications for cocaine use disorder II: Choice between intravenous cocaine and money in humans.
A medication for treating cocaine use disorder has yet to be approved. Laboratory-based evaluation of candidate medications in animals and humans is a valuable means to demonstrate safety, tolerability and initial efficacy of potential medications. However, animal-to-human translation has been hampered by a lack of coordination. Therefore, we designed homologous cocaine self-administration studies in rhesus monkeys (see companion article) and human subjects in an attempt to develop linked, functionally equivalent procedures for research on candidate medications for cocaine use disorder.



Eight (N=8) subjects with cocaine use disorder completed 12 experimental sessions in which they responded to receive money ($0.01, $1.00 and $3.00) or intravenous cocaine (0, 3, 10 and 30mg/70kg) under independent, concurrent progressive-ratio schedules. Prior to the completion of 9 choice trials, subjects sampled the cocaine dose available during that session and were informed of the monetary alternative value.



The allocation of behavior varied systematically as a function of cocaine dose and money value. Moreover, a similar pattern of cocaine choice was demonstrated in rhesus monkeys and humans across different cocaine doses and magnitudes of the species-specific alternative reinforcers. The subjective and cardiovascular responses to IV cocaine were an orderly function of dose, although heart rate and blood pressure remained within safe limits.



These coordinated studies successfully established drug versus non-drug choice procedures in humans and rhesus monkeys that yielded similar cocaine choice behavior across species. This translational research platform will be used in future research to enhance the efficiency of developing interventions to reduce cocaine use.
Department of Behavioral Science, University of Kentucky College of Medicine, Medical Behavioral Science Building, 1100 Veterans Dr., Lexington, KY 40536-0086, United States; Department of Psychology, University of Kentucky College of Arts and Sciences, Kastle Hall, Lexington, KY 40506-0044, United States; Department of Psychiatry, University of Kentucky College of Medicine, 3470 Blazer Pkwy, Lexington, KY 40509-1810, United States. Electronic address: jalile2@email.uky.edu.
Joshua A
JA
Lile
Department of Behavioral Science, University of Kentucky College of Medicine, Medical Behavioral Science Building, 1100 Veterans Dr., Lexington, KY 40536-0086, United States; Department of Psychology, University of Kentucky College of Arts and Sciences, Kastle Hall, Lexington, KY 40506-0044, United States; Department of Psychiatry, University of Kentucky College of Medicine, 3470 Blazer Pkwy, Lexington, KY 40509-1810, United States.
William W
WW
Stoops
Department of Behavioral Science, University of Kentucky College of Medicine, Medical Behavioral Science Building, 1100 Veterans Dr., Lexington, KY 40536-0086, United States; Department of Psychology, University of Kentucky College of Arts and Sciences, Kastle Hall, Lexington, KY 40506-0044, United States; Department of Psychiatry, University of Kentucky College of Medicine, 3470 Blazer Pkwy, Lexington, KY 40509-1810, United States.
Craig R
CR
Rush
Department of Pharmacology and Toxicology, Virginia Commonwealth University Medical Center, 410 N. 12th St., Richmond, VA 23298-0613, United States.
S Stevens
SS
Negus
Department of Psychiatry, University of Kentucky College of Medicine, 3470 Blazer Pkwy, Lexington, KY 40509-1810, United States; Department of Psychiatry, Washington University School of Medicine in St. Louis, 660 S. Euclid Ave., St. Louis, MO 6311, United States.
Paul E A
PE
Glaser
Department of Anesthesiology, University of Kentucky College of Medicine, Chandler Medical Center, 800 Rose St., Lexington, KY 40536, United States; Department of Surgery, University of Kentucky College of Medicine, Chandler Medical Center, 800 Rose St., Lexington, KY 40536, United States.
Kevin W
KW
Hatton
Department of Psychiatry, University of Kentucky College of Medicine, 3470 Blazer Pkwy, Lexington, KY 40509-1810, United States; Department of Internal Medicine, University of Kentucky College of Medicine, University Health Service, 830 South Limestone, Lexington, KY 40536-0284, United States.
Lon R
LR
Hays
D061605:Administration, Intravenous; D000328:Adult; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002755:Choice Behavior / Q000187:drug effects*; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D019970:Cocaine-Related Disorders / Q000523:psychology; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008253:Macaca mulatta; D008297:Male; D008875:Middle Aged; D012055:Reinforcement Schedule; D012054:Reinforcement, Psychology; D012646:Self Administration; D057170:Translational Research, Biomedical / Q000379:methods*; D055815:Young Adult
D003042:Cocaine
Cardiovascular; Choice; Monkey; Progressive-ratio; Reinforcing effects; Reverse translation; Subjective effects