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Adolescent cannabinoid exposure permanently suppresses cortical oscillations in adult mice.

ABSTRACT: Regular marijuana use during adolescence, but not adulthood, may permanently impair cognition and increase the risk for psychiatric diseases, such as schizophrenia. Cortical oscillations are integral for cognitive processes and are abnormal in patients with schizophrenia. We test the hypothesis that adolescence is a sensitive period because of the active development of cortical oscillations and neuromodulatory systems that underlie them. The endocannabinoid system upon which marijuana acts is one such system. Here we test the prediction that adolescent cannabinoid exposure alters cortical oscillations in adults. Using in vitro local field potential, in vivo electrocorticogram recordings and cognitive behavioral testing in adult mice, we demonstrate that chronic adolescent, but not adult, cannabinoid exposure suppresses pharmacologically evoked cortical oscillations and impairs working memory performance in adults. The later-maturing prefrontal cortex is more sensitive to adolescent exposure than the earlier-maturing, primary somatosensory cortex. These data establish a link between chronic adolescent cannabinoid exposure and alterations in adult cortical network activity that underlie cognitive processes.

SUBMITTER: Raver SM

PROVIDER: S-EPMC3799078 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

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Adolescent cannabinoid exposure permanently suppresses cortical oscillations in adult mice.

Raver Sylvina M SM Haughwout Sarah P SP Keller Asaf A

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 20130704 12

Regular marijuana use during adolescence, but not adulthood, may permanently impair cognition and increase the risk for psychiatric diseases, such as schizophrenia. Cortical oscillations are integral for cognitive processes and are abnormal in patients with schizophrenia. We test the hypothesis that adolescence is a sensitive period because of the active development of cortical oscillations and neuromodulatory systems that underlie them. The endocannabinoid system upon which marijuana acts is on ...[more]

PMID: 23822952

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Project description:IntroductionDuring adolescence, exposure to nicotine or cannabis independently induces effects on neuromaturation and later cognitive function. However, the potential effect of both drugs under co-use conditions has become of increasing concern given the prevalence of e-cigarettes, legalization of cannabis, and availability of synthetic "spice" cannabinoid agonists.Aims and methodsThe current studies investigated the effects of exposure to a cannabinoid receptor agonist (WIN55,212-2) and/or nicotine over a discrete time period in mid-adolescence on later intravenous nicotine self-administration in adult male and female mice. We further examined whether cannabinoid agonist administration in adulthood would alter nicotine reinforcement, with either acute or chronic pairing across 7 days.ResultsWe found that adult males exhibited increased nicotine self-administration at a lower, rewarding nicotine dose following adolescent cannabinoid exposure, either alone or with nicotine coadministration. In contrast, adult females demonstrated an opposing effect in which adolescent cannabinoid and nicotine coexposure resulted in decreased nicotine intake compared with the nicotine only and control groups. Furthermore, after maintaining nicotine self-administration across sessions, pretreatment with a low dose of the cannabinoid agonist decreased nicotine intake in both male and female control mice, and this lowering effect was evidenced after both acute and chronic treatment. However, the cannabinoid agonist was ineffective in altering nicotine intake in mice previously exposed to nicotine, cannabinoid agonist, or both during adolescence.ConclusionsThese data provide evidence that adolescent drug exposure can alter later nicotine reinforcement in a sex-specific manner and can further modulate the effectiveness of interventions in reducing nicotine intake during adulthood.ImplicationsThese studies demonstrate a significant impact of nicotine, cannabinoids, or coexposure on developmental processes during adolescence. Differential effects were observed within each sex, with opposing results found for cannabinoid exposure on nicotine intake in males and females. Intriguingly, we also evidenced resistance to the lowering effects of a cannabinoid agonist on nicotine intake in adulthood based on adolescent drug exposure. Thus, these findings have important implications for our understanding of the impact of nicotine and cannabinoids (eg, Δ9-tetrahydrocannabinol (THC) and synthetic "spice" cannabinoids) during development, with further implications for the effectiveness of therapeutic interventions based on prior drug exposure in youth.

Dataset Information

Adolescent cannabinoid exposure permanently suppresses cortical oscillations in adult mice.

Publications

Adolescent cannabinoid exposure permanently suppresses cortical oscillations in adult mice.

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