Abstract
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.
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Acknowledgements
Startup funds from the Psychology Department of the University of Illinois at Urbana-Champaign (to NCL) and NIH grants R03DA043701 (to NCL), R01GM115584-01A1, and R03DA042365-01A1 (to AD) supported this study. We thank Dr. Lucas Li of the Roy J. Carver Metabolomics Center (UIUC) for performing the LC-MS/MS analyses. We acknowledge the technical assistance of Firmino Pinto, Charles Shoemaker, Jacqueline Sanchez, and Sheel Vasavada and are grateful to Dr. Justin Rhodes who provided access to the TopScan software. Portions of this work were presented at the 41st annual scientific meeting of the Research Society on Alcoholism in San Diego, CA, USA.
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Nelson, N.G., Law, W.X., Weingarten, M.J. et al. Combined ∆9-tetrahydrocannabinol and moderate alcohol administration: effects on ingestive behaviors in adolescent male rats. Psychopharmacology 236, 671–684 (2019). https://doi.org/10.1007/s00213-018-5093-3
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DOI: https://doi.org/10.1007/s00213-018-5093-3