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

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.

SUBMITTER: Nelson NG

PROVIDER: S-EPMC6401297 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Combined ∆<sup>9</sup>-tetrahydrocannabinol and moderate alcohol administration: effects on ingestive behaviors in adolescent male rats.

Nelson Nnamdi G NG Law Wen Xuan WX Weingarten Michael J MJ Carnevale Lauren N LN Das Aditi A Liang Nu-Chu NC

Psychopharmacology 20181110 2

<h4>Rationale</h4>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 ∆<sup>9</sup>-tetrahydrocannabinol (THC), the main psychoactive constitute of marijuana, alters feeding behavior and cognition differently from either drug alone.<h4>Methods</h4>Male rats received daily THC (3-20 mg/kg/day) or oil vehicle through subcutaneous inje ...[more]

PMID: 30415276

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Project description:BACKGROUND:Cannabinoids and their principle psychoactive target, the cannabinoid type 1 receptor (CB1R), impact a number of alcohol-related properties, and although alcohol and cannabis are often co-used, particularly in adolescence, few animal models of this phenomenon exist. We modeled the co-use of alcohol and ?9 -tetrahydrocannabinol (THC) in adolescent mice using ingestive methods popular during this developmental period in humans, namely binge-drinking and edible THC. With this model, we assessed levels of use, acute effects, and tolerance to each substance. METHODS:Adolescent male C57BL/6J mice had daily, limited access to 1 of 2 edible doughs (THC or control), to 1 of 2 fluids (ethanol (EtOH) or water), and in 1 of 2 orders (dough-fluid or fluid-dough). Home cage locomotor activity was recorded both during access and after access. On the day following the final access session, a subset of mice were assessed for functional and metabolic tolerance to alcohol using accelerating rotarod and blood EtOH concentrations, respectively. The remaining mice were assessed for tolerance to THC-induced hypothermia, and whole-brain CB1R expression was assessed in all mice. RESULTS:EtOH intake was on par with levels previously reported in adolescent mice. Edible THC was well-consumed, but consumption decreased at the highest dose provided. Locomotor activity increased following EtOH intake and decreased following edible THC consumption, and edible THC increased fluid intake in general. The use of alcohol produced neither functional nor metabolic tolerance to an alcohol challenge. However, the use of edible THC impaired subsequent drug-free rotarod performance and was associated with a reduction in THC's hypothermic effect. CONCLUSIONS:Adolescent mice self-administered both alcohol and edible THC to a degree sufficient to acutely impact locomotor activity. However, only edible THC consumption had lasting effects during short-term abstinence. Thus, this adolescent co-use model could be used to explore sex differences in self-administration and the impact substance co-use might have on other domains such as mood and cognition.

Dataset Information

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

Publications

Combined ∆<sup>9</sup>-tetrahydrocannabinol and moderate alcohol administration: effects on ingestive behaviors in adolescent male rats.

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