TY  - JOUR
PY  - 2017//
TI  - Chronic exposure to cannabinoids during adolescence causes long-lasting behavioral deficits in adult mice
JO  - Addiction biology
A1  - Tomas-Roig, J.
A1  - Benito, E.
A1  - Agis-Balboa, R. C.
A1  - Piscitelli, F.
A1  - Hoyer-Fender, S.
A1  - Di Marzo, V.
A1  - Havemann-Reinecke, U.
SP  - 1778
EP  - 1789
VL  - 22
IS  - 6
N2  - 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.<br><br>© 2016 The Authors Addiction Biology published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.<p />  <p>Language: en</p>
LA  - en
SN  - 1355-6215
UR  - http://dx.doi.org/10.1111/adb.12446
ID  - ref1
ER  -