Background 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. Methods 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 30 mg/70 kg) 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. Results 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. Conclusions 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.
|Number of pages||9|
|Journal||Drug and Alcohol Dependence|
|State||Published - Aug 1 2016|
Bibliographical noteFunding Information:
This research and the preparation of this manuscript were supported by grants awarded to Dr. Joshua Lile ( National Institute on Drug Abuse grants K02 DA031766 and R01 DA033364 ) as well as the University of Kentucky Center for Clinical and Translational Science (National Center for Advancing Translational Sciences grant UL1TR000117 ). These funding sources had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication.
© 2016 Elsevier Ireland Ltd
- Reinforcing effects
- Reverse translation
- Subjective effects
ASJC Scopus subject areas
- Psychiatry and Mental health
- Pharmacology (medical)