Dataset Information

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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Publications

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:BackgroundCannabinoids 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.MethodsAdolescent 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.ResultsEtOH 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.ConclusionsAdolescent 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.

Project description:Every fifteen minutes, a baby is born in the U.S. experiencing neonatal opioid withdrawal syndrome (NOWS). Since 2004, the rate of NOWS has increased 7-fold. Clinical studies have established intrauterine exposure to drugs of abuse as a risk factor for adverse health outcomes in adult life, including the propensity for future illicit drug use. Despite extensive knowledge about common mechanisms of action in the neural circuitry that drives opioid and alcohol reward, there is little data on the risks that those born with NOWS face regarding alcohol use later in life. Here, we investigate the impact of perigestational opioid exposure (POE) on the mesolimbic reward system of male and female Sprague Dawley rats at postnatal and adolescent ages. Our laboratory has developed a clinically relevant model for morphine exposure spanning pre-conception to the first week of life. Using this model, we found that POE increased alcohol consumption in female rats under noncontingent conditions, and inversely, reduced alcohol consumption in both male and female rats during operant conditioning sessions. Operant responding was also reduced for sucrose, suggesting that the impact of POE on reward-seeking behaviors is not limited to drugs of abuse. Expression of µ-opioid receptors was also significantly altered in the nucleus accumbens and medial habenula, regions previously shown to play a significant role in reward/aversion circuitry.Significance statementEarly life exposure to opioids is known to alter future drug behavior in rats. In the present study, female rats exposed to morphine via their mothers throughout and after pregnancy exhibited increased alcohol consumption when allowed to consume freely. During operant conditioning, however, male and female rats exposed to gestational morphine decreased consumption of alcohol as well as sucrose. We also observed that gestational morphine exposure altered µ-opioid receptor expression in reward-related brain regions. Our study provides the first evidence of changes in alcohol-directed reward behavior in a gestational opioid exposure rat model.

Project description:BackgroundSex is an important factor in the progression and treatment of alcohol addiction, and therapeutic approaches may have to be tailored to potential sex differences. This highlights the importance of understanding sex differences in behaviors that reflect key elements of clinical alcohol addiction, such as continued use despite negative consequences ("compulsive use"). Studies in experimental animals can help provide an understanding of the role sex plays to influence these behaviors.MethodsLarge populations of genetically heterogeneous male and female Wistar rats were tested in an established model of compulsive alcohol self-administration, operationalized as alcohol responding despite contingent foot shock punishment. We also tested baseline (fixed ratio, unpunished) operant alcohol self-administration, motivation to self-administer alcohol (progressive ratio), and temporal discounting for alcohol reward. In search of predictors of compulsivity, animals were screened for novelty-induced place preference, anxiety-like behavior, pain sensitivity and corticosterone levels. The estrous cycle was monitored throughout the study.ResultsUnpunished self-administration of alcohol did not differ between males and females when alcohol intake was corrected for body weight. Overall, females showed higher levels of compulsive responding for alcohol. Compulsive response rates showed bimodal distributions in male but not in female rats when intermediate shock intensities were used (0.2 and 0.25 mA); at higher shock intensities, responding was uniformly suppressed in both males and females. We also found less steep discounting in females when alcohol was devalued by delaying its delivery. Males exhibited a stronger motivation to obtain alcohol under unpunished conditions, while females showed higher corticosterone levels at baseline. Factor analysis showed that an underlying dimension related to stress and pain predicted compulsivity in females, while compulsivity in males was predicted by a reward factor. We did not find differences in alcohol-related behaviors throughout the various stages of the estrous cycle.ConclusionsOur results suggest that mechanisms promoting compulsivity, a key feature of alcohol addiction, likely differ between males and females. This underscores the importance of considering sex as a biological variable in both preclinical and clinical research, and has potential treatment implications in alcohol addiction.

Dataset Information

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

Rationale

Methods

Results

Conclusion

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

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

Rationale

Methods

Results

Conclusion

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

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