Adolescent THC exposure in female rats leads to cognitive deficits through a mechanism involving chromatin modifications in the prefrontal cortex

Prini, Pamela; Rusconi, Francesco; Zamberletti, Erica; Gabaglio, Marina; Penna, Federica; Fasano, Mauro; Battaglioli, Elena; Parolaro, Daniela; Rubino, Tiziana

doi:10.1503/jpn.170082

Cited by 59 publications

(51 citation statements)

References 57 publications

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“…Interestingly, total FC CB1 receptors remain unchanged in adult female rodents following adolescent exposure to a CB1 receptor agonist (Lovelace et al 2015), suggesting that persistent cognitive deficits in FC-mediated tasks produced by adolescent exposure to a CB1 agonist may be mediated by downstream systems such as glutamate and GABA and not the endocannabinoid system. Moreover, recent findings indicate that repetitive THC exposure during adolescence, but not adulthood, alters adult prefrontal cortex gene expression associated with synaptic plasticity and GABAergic and glutamatergic systems in female rats (Prini et al 2018). Nevertheless, alterations in longterm depression in the FC of adult female rodents exposed to a CB1 agonist during adolescence is prevented by inhibiting the breakdown of the endogenous endocannabinoid 2-arachidonyglycerol (Lovelace et al 2015).…”

Section: Impact Of Adolescent Marijuana Exposure On the Fc And Behaviormentioning

confidence: 99%

The long-term cognitive consequences of adolescent exposure to recreational drugs of abuse

Mooney‐Leber

Gould

2018

Learn. Mem.

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During adolescence, the brain continues to undergo vital developmental processes. In turn, complex behavioral and cognitive skills emerge. Unfortunately, neurobiological development during adolescence can be influenced by environmental factors such as drug exposure. Engaging in drug use during adolescence has been a long-standing health concern, especially how it predicts or relates to drug using behavior later in life. However, recent findings suggest that other behavioral domains, such as learning and memory, are also vulnerable to adolescent drug use. Moreover, it is becoming increasingly apparent that deficits in learning and memory following adolescent drug use endure into adulthood, well after drug exposure has subsided. Although persistent effects suggest an interaction between drug exposure and ongoing development during adolescence, the exact acute and long-term consequences of adolescent drug exposure on substrates of learning and memory are not fully understood. Thus, this review will summarize human and animal findings on the enduring cognitive deficits due to adolescent drug exposure. Moreover, due to the fact that adolescents are more likely to consume drugs of abuse legally available to adults, this review will focus on alcohol, nicotine, and marijuana. Further, given the critical role of the frontal cortex and hippocampus in various learning and memory domains, the impact adolescent use of the previous listed drugs on the neurobiology within these regions will also be discussed.

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Section: Impact Of Adolescent Marijuana Exposure On the Fc And Behaviormentioning

confidence: 99%

The long-term cognitive consequences of adolescent exposure to recreational drugs of abuse

Mooney‐Leber

Gould

2018

Learn. Mem.

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“…L'exposition au THC induit des déficits cognitifs, qui sont prévenus par le blocage de la méthylation de l'histone au moyen de la chaetocine, un inhibiteur de SUV39H1. Il est à noter que l'exposition au THC de rats femelles adultes se traduit par un accroissement (+54 %) de l'histone H3K9me3, à la 2 e heure après la dernière injection de THC, mais elle ne persiste pas à la 24 e heure, beaucoup moins de gènes étant réprimés comparativement à l'exposition au THC chez l'adolescent, avec aussi de moindres déficits cognitifs [34]. L'administration de THC à des rats mâles, à la période de leur adolescence (à partir de leur 28 e jour post-natal, tous les 3 jours, 8 injections au total), a été suivie d'une étude de l'architecture morphologique et du profil transcriptionnel de la couche III des neurones pyramidaux du cortex préfrontal [35].…”

Section: Système Immunitaireunclassified

Les effets épigénétiques du cannabis/tétrahydrocannabinol

Costentin

2020

Bulletin de l'Académie Nationale de Médecine

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Étant donné le contexte sanitaire épidémique lié au Covid-19 du mois de mars 2020, la présentation orale de cette communication en séance à l'Académie a été reportée. RésuméLa diffusion, sur un mode quasi pandémique, du cannabis chez les adolescents et adultes jeunes, spécialement en France, justifie l'attention portée aux conséquences, non seulement aiguës, mais également différées de cette intoxication. Dans cette dernière éventualité interviennent des mécanismes épigénétiques. On rappellera d'abord différents types de modifications épigénétiques portant soit sur les histones de la chromatine, principalement des méthylations ou des acétylations ; soit sur l'ADN, par méthylation des cytosines. Des modifications de ce type suscitées par le tétrahydrocannabinol/THC du cannabis peuvent intervenir : soit au niveau des gamètes avant la procréation ; soit sur le foetus pendant la gestation ; soit à différents moments de la vie de l'individu. À certaine de ces modifications épigénétiques est associé un accroissement de la vulnérabilité aux toxicomanies, impliquant les récepteurs D2 de la dopamine dans le noyau accumbens ; une surexpression de la synthèse du précurseur des enképhalines ; des modifications : des récepteurs CB1 des endocannabinoïdes ; des récepteurs de l'acide glutamique ; du GABA ; de protéines impliquées dans la plasticité synaptique, etc. Des modifications épigénétiques peuvent aussi affecter : le système immunitaire ; les activités cognitives ; le développement d'affections psychiatriques en relation avec des perturbations de la maturation cérébrale. Les connaissances qui s'accumulent à cet égard vont à l'opposé de la banalisation ambiante du cannabis. Elles imposent d'alerter les pouvoirs publics et le public, spécialement les jeunes, sur les risques associées à la consommation de cette drogue. SummaryThe almost pandemic spread of cannabis among adolescents and young adults, especially in France, justifies the attention given to the consequences, not only acute but also delayed, of this intoxication.Page 2 of 15 J o u r n a l P r e -p r o o f 2 In the latter case, epigenetic mechanisms occur. We will first recall various types of epigenetic modifications involving either chromatin histones, mainly methylations or acetylations; either DNA, by methylation of cytosines. Such modifications caused by the tetrahydrocannabinol/THC of cannabis can intervene: either at the level of gametes before procreation, or at different points of the life cycle.These epigenetic modifications are associated with an increase in vulnerability to drug addiction, involving dopamine D2 receptors in the nucleus accumbens, overexpression of enkephalin precursor synthesis, modifications of: CB1 receptors of endocannabinoids, glutamic acid receptors, GABA receptors, proteins involved in synaptic plasticity ... These changes can also affect: immune system, cognitive activities, development of psychiatric diseases, related to disturbances of brain maturation.The knowledge that accumulates in this respect is the opposite of the ambie...

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“…To date, the precise mechanisms explaining the inheritance of behavioural and physiological traits are still ambiguous in particular in the context of paternal cannabinoids abuse (ZHANG and DUAN, 2017). Nevertheless, several epigenetic changes have been correlated to dysregulated gene expression pattern in animal models of chronic exposure to cannabinoids during adolescence, such as DNA methylation, histone modifications and RNA interference (Szutorisz and Hurd, 2017, 2016; Zumbrun et al, 2015; Prini et al, 2018). Also, it has been shown that some epigenetic changes can escape the epigenomic reprogramming that occurs during gametogenesis and fertilization and affects behaviour and vulnerability to stress in subsequent generations (Prini et al, 2018; Jabbar et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

“…Nevertheless, several epigenetic changes have been correlated to dysregulated gene expression pattern in animal models of chronic exposure to cannabinoids during adolescence, such as DNA methylation, histone modifications and RNA interference (Szutorisz and Hurd, 2017, 2016; Zumbrun et al, 2015; Prini et al, 2018). Also, it has been shown that some epigenetic changes can escape the epigenomic reprogramming that occurs during gametogenesis and fertilization and affects behaviour and vulnerability to stress in subsequent generations (Prini et al, 2018; Jabbar et al, 2016). Moreover, unlike RNA interference and histone modifications, DNA methylation is presumably a more static epigenetic mark and possibly transgenerationaly transferable (Williams and Gehring, 2017).…”

Section: Introductionmentioning

confidence: 99%

Behavioural and epigenetic effects of paternal exposure to cannabinoids during adolescence on offspring vulnerability to stress

Andaloussi

Taghzouti

Abboussi

2018

Intl J of Devlp Neuroscience

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Chronic cannabinoid exposure during adolescence in male rats induces chronic cognitive and emotional impairments. However, the impact of this form of exposure on offspring vulnerability to stress is unknown. The aim of this study was to evaluate the behavioural and epigenetic effects of stress in the offspring of male rats whose fathers were exposed to cannabinoids during adolescence. Male adolescent offspring of Win55,212‐2 (1.2 mg/kg) treated rats were exposed during one week to variable stressors and subjected to behavioural tests of anxiety and episodic‐like memory, followed by an assessment of global DNA methylation and expression of DNA methyltransferases enzymes DNMT1 and DNMT3a mRNA in the prefrontal cortex. Stress exposure induced a significant anxiogenic‐like effect but did not affect the episodic‐like memory in the offspring of Win55,212‐2 exposed fathers in comparison to the offspring of non‐exposed fathers. These behavioural changes were subsequent to a significant increase in global DNA methylation and DNMT1 and DNMTa3 transcription in the prefrontal cortex. These data suggest that the deleterious effect of chronic exposure to cannabinoids during adolescence are not limited to the exposed individuals but may increase the vulnerability to stress‐induced anxiety in the offspring and alter their epigenetic programming.

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Adolescent THC exposure in female rats leads to cognitive deficits through a mechanism involving chromatin modifications in the prefrontal cortex

Cited by 59 publications

References 57 publications

The long-term cognitive consequences of adolescent exposure to recreational drugs of abuse

The long-term cognitive consequences of adolescent exposure to recreational drugs of abuse

Les effets épigénétiques du cannabis/tétrahydrocannabinol

Behavioural and epigenetic effects of paternal exposure to cannabinoids during adolescence on offspring vulnerability to stress

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