Combined ∆9-tetrahydrocannabinol and moderate alcohol administration: effects on ingestive behaviors in adolescent male rats

• Published in: Psychopharmacology 2019-02, Vol.236 (2), p.671-684
• Main Authors: Nelson, Nnamdi G., Law, Wen Xuan, Weingarten, Michael J., Carnevale, Lauren N., Das, Aditi, Liang, Nu-Chu
• Format: Article
• Language: English
• Subjects: Adolescents; Age Factors; Alcohol Drinking - psychology; Alcohol Drinking - trends; Alcohol use; Alcoholic beverages; Alcohols; Animals; Biomedical and Life Sciences; Biomedicine; Cannabis; Cognitive ability; Dose-Response Relationship, Drug; Dronabinol - administration & dosage; Dronabinol - toxicity; Drug dosages; Energy balance; Ethanol - administration & dosage; Ethanol - toxicity; Exposure; Feeding behavior; Feeding Behavior - drug effects; Feeding Behavior - physiology; Feeding Behavior - psychology; Hedonic response; Hyperphagia - chemically induced; Hyperphagia - psychology; Injections, Subcutaneous; Male; Maze Learning - drug effects; Maze Learning - physiology; Memory tasks; Neurosciences; Original Investigation; Pharmacology/Toxicology; Psychiatry; Rats; Rats, Long-Evans; Rodents; Saccharin; Spatial analysis; Spatial discrimination; Spatial memory; Sucrose; Sugar; Teenagers; Tetrahydrocannabinol; THC; Weight Gain - drug effects; Weight Gain - physiology; Weight reduction
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-018-5093-3

Rationale Whereas co-use of alcohol and marijuana is prevalent in adolescents, the effects of such drug co-exposure on ingestive and cognitive behaviors remain largely unexplored. We hypothesized that co-exposure to alcohol and ∆ 9 -tetrahydrocannabinol (THC), the main psychoactive constitute of marijuana, alters feeding behavior and cognition differently from either drug alone. Methods Male rats received daily THC (3–20 mg/kg/day) or oil vehicle through subcutaneous injection or consumption of a cookie with access to saccharin or saccharin-sweetened alcohol during adolescence (P30–45). Barnes maze and sucrose preference tests were applied to assess spatial memory and behavioral flexibility and abstinence-related anhedonia, respectively. Results Subcutaneous THC did not affect alcohol intake but dose-dependently increased acute (3 h) chow intake and reduced weight gain. Moderate alcohol consumption reduced the acute hyperphagic effect of subcutaneous THC. By contrast, oral THC at a dose > 5 mg/kg robustly reduced alcohol intake without affecting 3-h chow intake. At this dose, some rats stopped consuming the THC-laced cookies. Furthermore, oral THC reduced weight gain, and co-exposure to alcohol alleviated this effect. Chronic subcutaneous, but not oral, THC reduced sucrose intake during abstinence. Neither treatment impaired cognitive behaviors in the Barnes maze. Conclusion Moderate alcohol and THC consumption can interact to elicit unique outcomes on ingestive behaviors and energy balance. Importantly, this study established a novel model of voluntary alcohol and THC consumption for studying mechanisms underlying the consequences of adolescent onset co-use of the two drugs.