Permanent suppression of cortical oscillations in mice after adolescent exposure to cannabinoids: receptor mechanisms.
Sylvina M Raver, Asaf Keller
Neuropharmacology November 2014 DOI: 10.1016/j.neuropharm.2014.07.006 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical experimental study Peer reviewed |
|---|---|
| Population | Adolescent and adult mice |
| Interventions | WIN55 212-2 |
| Duration | Six days of WIN55,212-2 in early adolescence; 20 days of THC in adolescence; oscillations measured in adults |
| Measures | pharmacologically-evoked oscillations in local field potentials (LFPs) in vitro |
| Topics | Cannabis |
| Keywords | Development Neural synchrony Schizophrenia |
| Key findings | The authors report that cannabinoid exposure in adolescence durably suppresses cortical oscillations in adult mice, with WIN55,212-2 acting through CB1 receptors in medial prefrontal cortex and long-term THC acting through CB1 receptors in somatosensory cortex. They also report unexpected involvement of CB2 receptors in both regions and possible contributions of non-cannabinoid receptor targets in medial prefrontal cortex, and propose that CB1 receptor antagonists may counteract these effects. |
Abstract
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 Δ(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.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.
Citations in the library
Cited by 8
- Long-term hippocampal interneuronopathy drives sex-dimorphic spatial memory impairment induced by prenatal THC exposure Neuropsychopharmacology January 26, 2020
- Cannabinoids and Vanilloids in Schizophrenia: Neurophysiological Evidence and Directions for Basic Research Frontiers in Pharmacology June 21, 2017
- Wpływ marihuany na aktywność elektryczną mózgu Kosmos April 11, 2020
- The Relationship Between Cannabinoids and Neural Oscillations: How Cannabis Disrupts Sensation, Perception, and Cognition Clinical EEG and Neuroscience November 25, 2022
- Mechanisms Contributing to Cognitive Deficits in Cannabis Users Neuropharmacology April 14, 2017
and 3 more in the library
Cites 4
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- Dynamic changes of the endogenous cannabinoid and opioid mesocorticolimbic systems during adolescence: THC effects. European Neuropsychopharmacology November 2008
- The diverse CB1 and CB2 receptor pharmacology of three plant cannabinoids: delta9-tetrahydrocannabinol, cannabidiol and delta9-tetrahydrocannabivarin. British Journal of Pharmacology January 2008