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Permanent suppression of cortical oscillations in mice after adolescent exposure
to cannabinoids: receptor mechanisms
#MMPMID25036610
Raver SM
; Keller A
Neuropharmacology
2014[Nov]; 86
(?): 161-73
PMID25036610
show ga
Marijuana use in adolescence, but not adulthood, may permanently impair cognitive
functioning and increase the risk of developing schizophrenia. Cortical
oscillations are patterns of neural network activity implicated in cognitive
processing, and are abnormal in patients with schizophrenia. We have recently
reported that cortical oscillations are suppressed in adult mice that were
treated with the cannabinoids WIN55,212-2 (WIN) or ?(9)tetrahydrocannabinol (THC)
in adolescence, but not adulthood. WIN and THC are cannabinoid-1 (CB1R) and CB2R
agonists, and also have activity at non-cannabinoid receptor targets. However, as
acute WIN and THC administration can suppress oscillations through CB1Rs, we
hypothesize that a similar mechanism underlies the permanent suppression of
oscillations by repeated cannabinoid exposure in adolescence. Here we test the
prediction that cannabinoid exposure in adolescence permanently suppresses
cortical oscillations by acting through CB1Rs, and that these suppressive effects
can be antagonized by a CB1R antagonist. We treated adolescent mice with various
cannabinoid compounds, and pharmacologically-evoked oscillations in local field
potentials (LFPs) in vitro in adults. We find that WIN exposure for six days in
early adolescence suppresses oscillations preferentially in adult medial
prefrontal cortex (mPFC) via CB1Rs, and that a similar CB1R mechanism accounts
for the suppressive effects of long-term (20 day) adolescent THC in adult
somatosensory cortex (SCx). Unexpectedly, we also find that CB2Rs may be involved
in the suppression of oscillations in both mPFC and SCx by long-term adolescent
cannabinoid exposure, and that non-cannabinoid receptors may also contribute to
oscillation suppression in adult mPFC. These findings represent a novel attempt
to antagonize the effects of adolescent cannabinoid exposure on neural network
activity, and reveal the contribution of non-CB1R targets to the suppression of
cortical oscillations.
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