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Cannabinoids reverse the effects of early stress on neurocognitive performance in adulthood

Early life stress (ES) significantly increases predisposition to psychopathologies. Cannabinoids may cause cognitive deficits and exacerbate the effects of ES. Nevertheless, the endocannabinoid system has been suggested as a therapeutic target for the treatment of stress- and anxiety-related disorde...

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Detalles Bibliográficos
Autores principales: Alteba, Shirley, Korem, Nachshon, Akirav, Irit
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4918780/
https://www.ncbi.nlm.nih.gov/pubmed/27317195
http://dx.doi.org/10.1101/lm.041608.116
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author Alteba, Shirley
Korem, Nachshon
Akirav, Irit
author_facet Alteba, Shirley
Korem, Nachshon
Akirav, Irit
author_sort Alteba, Shirley
collection PubMed
description Early life stress (ES) significantly increases predisposition to psychopathologies. Cannabinoids may cause cognitive deficits and exacerbate the effects of ES. Nevertheless, the endocannabinoid system has been suggested as a therapeutic target for the treatment of stress- and anxiety-related disorders. Here we examined whether cannabinoids administered during “late adolescence” (extensive cannabis use in humans at the ages 18–25) could reverse the long-term adverse effects of ES on neurocognitive function in adulthood. Male and female rats were exposed to ES during post-natal days (P) 7–14, injected with the cannabinoid CB1/2 receptor agonist WIN55,212-2 (WIN; 1.2 mg/kg, i.p.) for 2 wk during late adolescence (P45–60) and tested in adulthood (P90) for working memory, anxiety, and alterations in CB1 receptors (CB1r), and glucocorticoid receptors (GRs) in the stress circuit [hippocampus, prefrontal cortex (PFC), and basolateral amygdala (BLA)]. ES males and females exhibited impaired performance in short-term memory in adulthood in the spatial location and social recognition tasks; males were also impaired in the novel object recognition task. WIN administered during late adolescence prevented these stress-induced impairments and reduced anxiety levels. WIN normalized the ES-induced up-regulation in PFC-GRs and CA1–CB1r in females. In males, WIN normalized the ES-induced up-regulation in PFC-GR and down-regulation in BLA-CB1r. There is a crucial role of the endocannabinoid system in the effects of early life stress on behavior at adulthood. Differences in recognition memory and in the expression of GRs and CB1r in the fear circuit suggest sex differences in the mechanism underlying coping with stress.
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spelling pubmed-49187802017-07-01 Cannabinoids reverse the effects of early stress on neurocognitive performance in adulthood Alteba, Shirley Korem, Nachshon Akirav, Irit Learn Mem Research Early life stress (ES) significantly increases predisposition to psychopathologies. Cannabinoids may cause cognitive deficits and exacerbate the effects of ES. Nevertheless, the endocannabinoid system has been suggested as a therapeutic target for the treatment of stress- and anxiety-related disorders. Here we examined whether cannabinoids administered during “late adolescence” (extensive cannabis use in humans at the ages 18–25) could reverse the long-term adverse effects of ES on neurocognitive function in adulthood. Male and female rats were exposed to ES during post-natal days (P) 7–14, injected with the cannabinoid CB1/2 receptor agonist WIN55,212-2 (WIN; 1.2 mg/kg, i.p.) for 2 wk during late adolescence (P45–60) and tested in adulthood (P90) for working memory, anxiety, and alterations in CB1 receptors (CB1r), and glucocorticoid receptors (GRs) in the stress circuit [hippocampus, prefrontal cortex (PFC), and basolateral amygdala (BLA)]. ES males and females exhibited impaired performance in short-term memory in adulthood in the spatial location and social recognition tasks; males were also impaired in the novel object recognition task. WIN administered during late adolescence prevented these stress-induced impairments and reduced anxiety levels. WIN normalized the ES-induced up-regulation in PFC-GRs and CA1–CB1r in females. In males, WIN normalized the ES-induced up-regulation in PFC-GR and down-regulation in BLA-CB1r. There is a crucial role of the endocannabinoid system in the effects of early life stress on behavior at adulthood. Differences in recognition memory and in the expression of GRs and CB1r in the fear circuit suggest sex differences in the mechanism underlying coping with stress. Cold Spring Harbor Laboratory Press 2016-07 /pmc/articles/PMC4918780/ /pubmed/27317195 http://dx.doi.org/10.1101/lm.041608.116 Text en © 2016 Alteba et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first 12 months after the full-issue publication date (see http://learnmem.cshlp.org/site/misc/terms.xhtml). After 12 months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Research
Alteba, Shirley
Korem, Nachshon
Akirav, Irit
Cannabinoids reverse the effects of early stress on neurocognitive performance in adulthood
title Cannabinoids reverse the effects of early stress on neurocognitive performance in adulthood
title_full Cannabinoids reverse the effects of early stress on neurocognitive performance in adulthood
title_fullStr Cannabinoids reverse the effects of early stress on neurocognitive performance in adulthood
title_full_unstemmed Cannabinoids reverse the effects of early stress on neurocognitive performance in adulthood
title_short Cannabinoids reverse the effects of early stress on neurocognitive performance in adulthood
title_sort cannabinoids reverse the effects of early stress on neurocognitive performance in adulthood
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4918780/
https://www.ncbi.nlm.nih.gov/pubmed/27317195
http://dx.doi.org/10.1101/lm.041608.116
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