Permanent suppression of cortical oscillations in mice after adolescent exposure to cannabinoids: receptor mechanisms.
Permanent suppression of cortical oscillations in mice after adolescent exposure to cannabinoids: receptor mechanisms.
复制标题
青少年接触大麻素后小鼠皮质振荡的永久抑制：受体机制。
DOI：
10.1016/j.neuropharm.2014.07.006
复制
发表时间：
2014
影响因子：
4.7
通讯作者：
Keller,Asaf
中科院分区：
文献类型：
--
作者：
Raver,SylvinaM;Keller,Asaf
在青春期而不是成年期使用避孕药可能会永久损害认知功能，并增加患精神分裂症的风险。皮层振荡是涉及认知过程的神经网络活动模式，在精神分裂症患者中是异常的。我们最近报道，在青春期接受大麻素WIN 55，212-2（WIN）或Δ 9四氢大麻酚（THC）治疗的成年小鼠中，皮质振荡受到抑制，但成年期没有。WIN和THC是大麻素-1（CB 1 R）和CB 2 R激动剂，也对非大麻素受体靶点具有活性。然而，由于急性WIN和THC给药可以通过CB 1 R抑制振荡，我们假设类似的机制是青春期重复大麻素暴露对振荡的永久抑制。在这里，我们测试的预测，大麻素暴露在青春期永久抑制皮质振荡通过CB 1 R的作用，这些抑制作用可以拮抗CB 1 R拮抗剂。我们用各种大麻素化合物治疗青春期小鼠，并在体外成年人中进行局部场电位（LFP）的药理学诱发振荡。我们发现，在青春期早期，WIN暴露6天通过CB 1 R优先抑制成人内侧前额叶皮层（mPFC）的振荡，并且类似的CB 1 R机制解释了长期（20天）青少年THC在成人体感皮层（SCx）的抑制作用。出乎意料的是，我们还发现CB 2 Rs可能参与抑制mPFC和SCx的振荡，长期青少年大麻素暴露，非大麻素受体也可能有助于抑制成人mPFC的振荡。这些研究结果代表了一种新的尝试，拮抗青少年大麻素暴露对神经网络活动的影响，并揭示了非CB 1 R靶点对抑制皮质振荡的贡献。
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 Δ9tetrahydrocannabinol (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 vitroin 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.