Cannabinoid disruption of learning mechanisms involved in reward processing.
Cannabinoid disruption of learning mechanisms involved in reward processing.
复制标题
DOI：
10.1101/lm.046748.117
复制
发表时间：
2018-09
期刊：
影响因子：
--
通讯作者：
Hoffman AF
中科院分区：
文献类型：
--
作者：
Lupica CR;Hoffman AF
大麻及其衍生物和合成大麻素越来越多地用于医疗和娱乐目的，这使得人们对了解这类分子的成瘾潜力产生了浓厚的兴趣。据估计，约10%的大麻使用者最终会表现出对药物依赖的迹象，在美国，大麻使用障碍（CUD）的诊断正在增加。维持大麻使用的分子是Δ9-tetrahydrocannabinol （Δ9-THC），在过去二十年中，我们对其影响以及其他大麻素对大脑功能的影响的了解迅速扩大。此外，大脑内源性大麻素（内源性大麻素）系统的鉴定及其在生理和行为中的作用，表明这些脂质信号分子广泛参与调节中枢神经系统功能。在这里，我们研究了内源性大麻素在形成皮层和皮层下脑回路突触活动中的作用，并讨论了外源性大麻素（如Δ9-THC）与内源性大麻素系统相互作用以破坏神经网络振荡的机制。然后，我们探讨了大脑奖励回路中这种活动的相互作用的扰动如何导致学习受损。最后，我们提出外源性大麻素在皮层和皮层下回路中破坏细胞可塑性机制可能解释了在动物中建立可行的大麻素自我给药模型的困难。
The increasing use of cannabis, its derivatives, and synthetic cannabinoids for medicinal and recreational purposes has led to burgeoning interest in understanding the addictive potential of this class of molecules. It is estimated that ∼10% of marijuana users will eventually show signs of dependence on the drug, and the diagnosis of cannabis use disorder (CUD) is increasing in the United States. The molecule that sustains the use of cannabis is Δ9-tetrahydrocannabinol (Δ9-THC), and our knowledge of its effects, and those of other cannabinoids on brain function has expanded rapidly in the past two decades. Additionally, the identification of endogenous cannabinoid (endocannabinoid) systems in brain and their roles in physiology and behavior, demonstrate extensive involvement of these lipid signaling molecules in regulating CNS function. Here, we examine roles for endogenous cannabinoids in shaping synaptic activity in cortical and subcortical brain circuits, and we discuss mechanisms in which exogenous cannabinoids, such as Δ9-THC, interact with endocannabinoid systems to disrupt neuronal network oscillations. We then explore how perturbation of the interaction of this activity within brain reward circuits may lead to impaired learning. Finally, we propose that disruption of cellular plasticity mechanisms by exogenous cannabinoids in cortical and subcortical circuits may explain the difficulty in establishing viable cannabinoid self-administration models in animals.
登录
查看更多内容
影响因子：
6.9
作者：
Budney, AJ;Hughes, JR
通讯作者：
Hughes, JR
影响因子：
64.8
作者：
COBB, SR;BUHL, EH;SOMOGYI, P
通讯作者：
SOMOGYI, P
影响因子：
16.2
作者：
Cheer, Joseph F.;Aragona, Brandon J.;Wightman, R. Mark
通讯作者：
Wightman, R. Mark
影响因子：
16.2
作者：
Britt JP;Benaliouad F;McDevitt RA;Stuber GD;Wise RA;Bonci A
通讯作者：
Bonci A
影响因子：
5.3
作者：
Chevaleyre V;Piskorowski R
通讯作者：
Piskorowski R