Adolescence is an important ontogenetic period that is characterized by behaviors such as enhanced novelty-seeking, impulsivity, and reward preference, which can give rise to an increased risk for ...substance use. While substance use rates in adolescence are generally on a decline, the current rates combined with emerging trends, such as increases in e-cigarette use, remain a significant public health concern. In this review, we focus on the neurobiological divergences associated with adolescent substance use, derived from cross-sectional, retrospective, and longitudinal studies, and highlight how use of these substances during adolescence may relate to behavioral outcomes. Identifying and understanding the associations between adolescent substance use and changes in cognition, mental health, and future substance use risk may assist our understanding of the consequences of drug exposure during this critical window.
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
α knockout mouse line and ethanol two-bottle choice preference testing to show that disruption of
α reduces ethanol preference in male and female mice.
α 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
α may contribute to differences in alcohol drinking.
Adolescence is the transitional period between childhood and adulthood, during which extensive brain development occurs. Since this period also overlaps with the initiation of drug use, it is ...important to consider how substance use during this time might produce long-term neurobiological alterations, especially against the backdrop of developmental changes in neurotransmission. Alcohol, cannabis, nicotine, and opioids all produce marked changes in the expression and function of the neurotransmitter and receptor systems with which they interact. These acute and chronic alterations also contribute to behavioral consequences ranging from increased addiction risk to cognitive or neuropsychiatric behavioral dysfunctions. The current review provides an in-depth overview and update of the developmental changes in neurotransmission during adolescence, as well as the impact of drug exposure during this neurodevelopmental window. While most of these factors have been studied in animal models, which are the focus of this review, future longitudinal studies in humans that assess neural function and behavior will help to confirm pre-clinical findings. Furthermore, the neural changes induced by each drug should also be considered in the context of other contributing factors, such as sex. Further understanding of these consequences can help in the identification of novel approaches for preventing and reversing the neurobiological effects of adolescent substance use.
Cannabis and alcohol co-use is prevalent in adolescence, but the long-term behavioural effects of this co-use remain largely unexplored. The aim of this study is to investigate the effects of ...adolescent alcohol and Δ9-tetrahydracannabinol (THC) vapour co-exposure on cognitive- and reward-related behaviours. Male Sprague-Dawley rats received vapourized THC (10 mg vapourized THC/four adolescent rats) or vehicle every other day (from post-natal day (PND) 28–42) and had continuous voluntary access to ethanol (10% volume/volume) in adolescence. Alcohol intake was measured during the exposure period to assess the acute effects of THC on alcohol consumption. In adulthood (PND 56+), rats underwent behavioural testing. Adolescent rats showed higher alcohol preference, assessed using the two-bottle choice test, on days on which they were not exposed to THC vapour. In adulthood, rats that drank alcohol as adolescents exhibited short-term memory deficits and showed decreased alcohol preference; on the other hand, rats exposed to THC vapour showed learning impairments in the delay-discounting task. Vapourized THC, alcohol or their combination had no effect on anxiety-like behaviours in adulthood. Our results show that although adolescent THC exposure acutely affects alcohol drinking, adolescent alcohol and cannabis co-use may not produce long-term additive effects.
•Co-use of alcohol and cannabis is prevalent amongst adolescents.•Long-term effects of alcohol and cannabis co-use on behaviour are not well understood.•Adolescent rats showed greater alcohol preference during acute THC abstinence.•Vapourized THC and alcohol co-exposure may not produce additive behavioural effects.
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