Browsing by Author "Hernandez, Maribel"

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    Assessment of Acute Motor Effects and Tolerance Following Self‐Administration of Alcohol and Edible ∆9‐Tetrahydrocannabinol in Adolescent Male Mice
    (Wiley, 2019-11) Smoker, Michael P.; Hernandez, Maribel; Zhang, Yanping; Boehm, Stephen L., II; Psychology, School of Science
    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.
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    Sex and Genetic Differences in Behavioral Engagement of Crossed High Alcohol‐Preferring and Low Alcohol‐Preferring Mice
    (Wiley, 2025) Starski, Phillip; Siegle, Addyson; White, Danielle; Paras, Bea; Tham, Christy; Hernandez, Maribel; Zareb, Alecsander; Grahame, Nicholas; Boehm, Stephen L., II; Hopf, Frederic; Psychiatry, School of Medicine
    Excessive levels of alcohol consumption play a major role in numerous alcohol-related harms, including a heightened risk of developing problematic drinking behaviors. Those who develop alcohol use disorder (AUD) often struggle with persistent difficulties in controlling their drinking, experience withdrawal symptoms, and engage in risky behaviors that pose danger to themselves and others. Advances in treating AUD may be supported by identifying specific cognitive and emotional factors that drive excessive alcohol consumption. Recognizing reliable behavioral biomarkers is instrumental in assessing the risk of developing alcohol problems and preventative care strategies. This study investigates innate behavioral differences associated with genetic predisposition for alcohol use by comparing crossed high alcohol-preferring (cHAP) and low alcohol-preferring (LAP) mice. Since there have been links between heightened impulsivity and excessive alcohol use, we hypothesized that cHAP mice would exhibit higher levels of impulsivity compared to LAPs. No significant differences were found in impulsivity between the mouse lines or sexes. cHAPs adapted to shorter stimulus durations (SDs), whereas LAPs showed a marked decline in correct responses and an increase in omission rates as task difficulty increased. Significant sex differences within the cHAP line were found, with females demonstrating higher accuracy, lower correct latency, and increased perseveration. This behavior points to potential sex-specific neural activation in cognitive processing areas. Future studies should explore salient brain regions to understand their roles in behavioral regulation and sex-specific responses to challenges. This study provides a foundation for exploring the interaction of genetic predisposition, sex differences, and neural mechanisms in alcohol preference and behavior.