Introduction Co-occurrence of e-cigarette use and alcohol consumption during adolescence is frequent. Here, we examined whether adolescent co-exposure to alcohol drinking and vaporized nicotine would impact reward- and cognition-related behaviors in adult male and female rats during adulthood. Methods Four groups of male and female Sprague Dawley rats (n=8-11/group/sex) received either nicotine (JUUL 5% nicotine pods) or vehicle vapor for 10 minutes daily between postnatal days 30-46, while having continuous voluntary access to ethanol and water during this time in a two-bottle preference design. Upon reaching adulthood, all rats underwent behavioral testing (i.e., Pavlovian conditioned approach testing, fear conditioning and a two-bottle alcohol preference). Results A sex-dependent effect, not related to adolescent nicotine or alcohol exposure, on alcohol drinking in adulthood was found, such that females had a higher intake and preference for alcohol compared to males; both male and female adult rats also had greater alcohol preference compared to their alcohol preference as adolescents. Male rats exposed to vaporized nicotine with or without alcohol drinking during adolescence exhibited altered reward-related learning in adulthood, evidenced by enhanced levels of sign-tracking behavior. Male rats that drank alcohol with or without nicotine vapor in adolescence showed deficits in associative fear learning and memory as adults. In contrast, these effects were not seen in female rats exposed to alcohol and nicotine vapor during adolescence. Conclusions The present study provides evidence that co-exposure to alcohol and vaporized nicotine during adolescence in male, but not female, rats produces long-term changes in reward- and cognition-related behaviors. Implications These findings enhance our understanding of the effects of alcohol drinking and nicotine vapor exposure in adolescence. Moreover, they highlight potential sex differences that exist in the response to alcohol and nicotine vapor, underscoring the need for follow-up studies elucidating the neurobiological mechanisms that drive these sex differences, as well as the long-term effects of alcohol and nicotine vapor use.
Alcohol use is a contributor in the premature deaths of approximately 3 million people annually. Among the risk factors for alcohol misuse is circadian rhythm disruption; however, this connection remains poorly understood. Inhibition of the circadian nuclear receptor REV-ERBα is known to disrupt molecular feedback loops integral to daily oscillations, and impact diurnal fluctuations in the expression of proteins required for reward-related neurotransmission. However, the role of REV-ERBα in alcohol and substance use-related phenotypes is unknown. Herein, we used a Rev-erbα knockout mouse line and ethanol two-bottle choice preference testing to show that disruption of Rev-erbα reduces ethanol preference in male and female mice. Rev-erbα null mice showed the lowest ethanol preference in a two-bottle choice test across all genotypes, whereas there were no ethanol preference differences between heterozygotes and wildtypes. In a separate experiment, alcohol-consuming wildtype C57Bl/6N mice were administered the REV-ERBα/β inhibitor SR8278 (25 mg/kg or 50 mg/kg) for 7 days and alcohol preference was evaluated daily. No differences in alcohol preference were observed between the treatment and vehicle groups. Our data provides evidence that genetic variation in REV-ERBα may contribute to differences in alcohol drinking.
Accidental exposure to D9-tetrahydrocannabinol (THC)-containing edible cannabis, leading to cannabis poisoning, is common in children and pets; however, the neural mechanisms underlying these poisonings remain unknown. Therefore, we examined the effects of acute edible cannabis-induced poisoning on neural activity and behavior. Adult Sprague-Dawley rats (6 males, 7 females) were implanted with electrodes in the prefrontal cortex (PFC), dorsal hippocampus (dHipp), cingulate cortex (Cg), and nucleus accumbens (NAc). Cannabis poisoning was then induced by exposure to a mixture of Nutella (6 g/kg) and THC-containing cannabis oil (20 mg/kg). Subsequently, cannabis tetrad and neural oscillations were examined 2, 4, 8, and 24 h after THC exposure. In another cohort (16 males, 15 females), we examined the effects of cannabis poisoning on learning and prepulse inhibition, and the serum and brain THC and 11-hydroxy-THC concentrations. Cannabis poisoning resulted in sex differences in brain and serum THC and 11-hydroxy-THC levels over a 24-h period. It also caused gamma power suppression in the Cg, dHipp, and NAc in a sex- and time-dependent manner. Cannabis poisoning also resulted in hypolocomotion, hypothermia, and anti-nociception in a time dependent manner and impairments in learning and prepulse inhibition. Our results suggest that the impairments in learning and information processing may be due to the decreased gamma power in the dHipp and PFC. Additionally, most of the changes in neural activity and behavior appear 2 hours after ingestion, suggesting that interventions at or before this time might be effective in reversing or reducing the effects of cannabis poisoning.
Introduction: Co-occurrence of e-cigarette use and alcohol consumption during adolescence is frequent. However, little is known about their long-lasting effects when combined. Here, we examined whether adolescent co-exposure to alcohol drinking and vapourized nicotine would impact reward- and cognition-related behaviours in adult male and female rats during adulthood. Methods: Four groups of male and female Sprague Dawley rats (n=8-11/group/sex) received either nicotine (JUUL 5% nicotine pods) or vehicle vapour daily between postnatal days 30-46, while having continuous voluntary access to ethanol and water during this time in a two-bottle preference design. Upon reaching adulthood, rats underwent behavioural testing utilizing Pavlovian conditioned approach testing, fear conditioning and a two-bottle alcohol preference test. Results: A sex-dependent effect was found in the two-bottle preference test in adulthood such that females had a higher intake and preference for alcohol compared to males regardless of adolescent exposure; both male and female adult rats had greater alcohol preference compared to adolescents. Male rats exposed to vapourized nicotine with or without alcohol drinking during adolescence exhibited altered reward-related learning in adulthood, evidenced by enhanced levels of sign-tracking behaviour. Male rats that drank alcohol with or without nicotine vapour in adolescence showed deficits in associative fear learning and memory as adults. In contrast, these effects were not seen in female rats exposed to alcohol and nicotine vapour during adolescence. Conclusions: The present study provides evidence that co-exposure to alcohol and vapourized nicotine during adolescence in male, but not female, rats produces long-term changes in reward- and cognition-related behaviours.
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