Journal
NEUROPSYCHOPHARMACOLOGY
Volume 42, Issue 7, Pages 1522-1530Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/npp.2017.2
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Funding
- NIH/NIDA [R37 DA10584, P50 DA06634, F31 DA041825, T32 AA-007565]
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Reinforcing effects of.9-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 mu g/ kg, i. v.) and THC (3.0300 mu g/ 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 mu g/kg) functioned as a reinforcer in three monkeys, whereas THC (0.01-10 mu g/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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