Abstract
Reinforcing effects of Δ9-tetrahydrocannabinol (THC), the primary active ingredient in marijuana, as assessed with self-administration (SA), has only been established in New World primates (squirrel monkeys). The objective of this study was to investigate some experimental factors that may enhance intravenous SA of THC and the cannabinoid receptor (CBR) agonist CP 55 940 in Old World monkeys (rhesus and cynomolgus), a species that has been used extensively in biomedical research. In one experiment, male rhesus monkeys (N=9) were trained to respond under a fixed-ratio 10 schedule of food presentation. The effects of CP 55 940 (1.0–10 μg/kg, i.v.) and THC (3.0–300 μg/kg, i.v.) on food-maintained responding and body temperature were determined in these subjects prior to giving them access to self-administer each drug. Both drugs dose-dependently decreased food-maintained responding. CP 55 940 (0.001–3.0 μg/kg) functioned as a reinforcer in three monkeys, whereas THC (0.01–10 μg/kg) did not have reinforcing effects in any subject. CP 55 940 was least potent to decrease food-maintained responding in the monkeys in which CP 55 940 functioned as a reinforcer. Next, THC was administered daily to monkeys until tolerance developed to rate-decreasing effects. When THC SA was reexamined, it functioned as a reinforcer in three monkeys. In a group of cocaine-experienced male cynomolgus monkeys (N=4), THC SA was examined under a second-order schedule of reinforcement; THC functioned as reinforcer in two monkeys. These data suggest that SA of CBR agonists may be relatively independent of their rate-decreasing effects in Old World monkeys. Understanding individual differences in vulnerability to THC SA may lead to novel treatment strategies for marijuana abuse.
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Acknowledgements
We thank Michael Coller and Susan Nader for assistance throughout this project and Paul Czoty, Linda Porrino and Jenny Wiley for helpful discussions. We also thank Drs. Gianluigi Tanda and Amy Newman for their assistance with initiating these experiments. WSJ, TJM and MAN designed the studies. WSJ conducted the experiments and analyzed the data. WSJ, TJM and MAN wrote the manuscript.
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John, W., Martin, T. & Nader, M. Behavioral Determinants of Cannabinoid Self-Administration in Old World Monkeys. Neuropsychopharmacol 42, 1522–1530 (2017). https://doi.org/10.1038/npp.2017.2
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DOI: https://doi.org/10.1038/npp.2017.2
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