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. 2020 Apr;373(1):44-50.
doi: 10.1124/jpet.119.263707. Epub 2020 Jan 15.

Cannabinoid Modulation of Food-Cocaine Choice in Male Rhesus Monkeys

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Cannabinoid Modulation of Food-Cocaine Choice in Male Rhesus Monkeys

William S John et al. J Pharmacol Exp Ther. 2020 Apr.

Abstract

Marijuana and other cannabinoid compounds are widely used by cocaine users. Preclinical animal studies suggest that these compounds can increase the reinforcing effects of cocaine under some schedules of cocaine self-administration and reinstatement, but not in all cases. To date, no studies have used a food-cocaine concurrent choice procedure, which allows for assessment of drug effects on response allocation, not just changes in cocaine self-administration. The goal of the present study was to examine the effects of compounds differing in their efficacy at the cannabinoid receptor (CBR) on cocaine self-administration using a food-drug choice procedure in monkeys. Four adult male rhesus monkeys were trained to self-administer cocaine in the context of an alternative food (1.0-g banana-flavored pellets) reinforcer, such that complete cocaine dose-response curves (0, 0.003-0.1 mg/kg per injection) were determined each session. Monkeys were tested acutely with the CBR full agonist CP 55,940 (0.001-0.01 mg/kg); the CBR partial agonist Δ9-tetrahydrocannabinol (THC; 0.03-0.3 mg/kg), which is also the primary active ingredient in marijuana and the CBR antagonist rimonabant (0.3-3.0 mg/kg). Cocaine choice increased in a dose-dependent manner. Acute treatment with CP 55,940 decreased cocaine choice, whereas THC and rimonabant enhanced the reinforcing effects of cocaine. Chronic (7-day) treatment with CP 55,940 resulted in tolerance to the decreases in cocaine choice. These findings with Δ9-THC provide support for a potential mechanism for co-abuse of marijuana and cocaine. Additional research with chronic treatment with full CBR agonists on attenuating the reinforcing strength of cocaine is warranted. SIGNIFICANCE STATEMENT: Co-abuse of tetrahydrocannabinol and cocaine is a significant public health problem. The use of animal models allows for the determination of how cannabinoid receptor stimulation or blockade influences the reinforcing strength of cocaine.

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Figures

Fig. 1.
Fig. 1.
Effects of acute pretreatment of CP 55,940 (0.001–0.01 mg/kg, i.v.) (A), Δ9-THC (0.03–0.3 mg/kg, i.v.) (B), or rimonabant (0.3–3.0 mg/kg, i.v.) (C) on choice between cocaine and food in rhesus monkeys (n = 4). Ordinate: percent of reinforcers earned on the cocaine-associated switch. Abscissae: unit dose of cocaine in milligrams per kilogram per injection available as an alternative to a food pellet. All data represent means ± S.E.M. of four monkeys for at least two determinations of acute pretreatment of vehicle (filled symbols) or each test drug (open symbols). *P < 0.05 compared with respective vehicle pretreatment.
Fig. 2.
Fig. 2.
Effects on total reinforcers earned (A–C), food pellets earned (D–F), or total injections earned (G–I) of acute pretreatment of CP 55,940 (0.001–0.01 mg/kg, i.v.) (A, D, G), Δ9-THC (0.03–0.3 mg/kg, i.v.) (B, E, H), or rimonabant (0.3–3.0 mg/kg, i.v.) (C, F, I). Ordinate: number of respective reinforcer type earned out of a maximum of 10 available per component. Abscissae: unit dose of cocaine in milligrams per kilogram per injection available as an alternative to a food pellet. All data represent means ± S.E.M. of four monkeys for at least two determinations of acute pretreatment of vehicle (filled symbols) or each test drug (open symbols). *P < 0.05 compared with respective vehicle pretreatment.
Fig. 3.
Fig. 3.
Effects of acute (open triangles) and day 7 of chronic treatment (open squares) of CP 55,940 on percent cocaine choice. The dose of CP 55,940 was individually determined (see text). All data represent means ± S.E.M. of four monkeys. Other details are as described in Fig. 1. *P < 0.05 compared with respective vehicle pretreatment.

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