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Citation |
Tomas-Roig J, Benito E, Agis-Balboa RC, Piscitelli F, Hoyer-Fender S, Di Marzo V, Havemann-Reinecke U. Addict. Biol. 2017; 22(6): 1778-1789. |
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Affiliation |
Center Nanoscale Microscopy and Molecular Physiology of the Brain (CNMPB), Germany. |
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Copyright |
(Copyright © 2017, John Wiley and Sons) |
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DOI |
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PMID |
27578457 |
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Abstract |
Regular use of marijuana during adolescence enhances the risk of long-lasting neurobiological changes in adulthood. The present study was aimed at assessing the effect of long-term administration of the synthetic cannabinoid WIN55212.2 during adolescence in young adult mice. Adolescent mice aged 5 weeks were subjected daily to the pharmacological action of WIN55212.2 for 3 weeks and were then left undisturbed in their home cage for a 5-week period and finally evaluated by behavioral testing. Mice that received the drug during adolescence showed memory impairment in the Morris water maze, as well as a dose-dependent memory impairment in fear conditioning. In addition, the administration of 3 mg/kg WIN55212.2 in adolescence increased adult hippocampal AEA levels and promoted DNA hypermethylation at the intragenic region of the intracellular signaling modulator Rgs7, which was accompanied by a lower rate of mRNA transcription of this gene, suggesting a potential causal relation. Although the concrete mechanisms underlying the behavioral observations remain to be elucidated, we demonstrate that long-term administration of 3 mg/kg of WIN during adolescence leads to increased endocannabinoid levels and altered Rgs7 expression in adulthood and establish a potential link to epigenetic changes. Language: en |