Hashimotodani Yuki, Tanimura Asami, Kano Masanobu
Department of Neurophysiology, Division of Functional Biology, Graduate School of Medicine, University of Tokyo, 7-3-1, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Nihon Shinkei Seishin Yakurigaku Zasshi. 2011 Jun;31(3):105-9.
Marijuana smoking elicits various psychoactive effects through type 1 cannabinoid receptors (CB(1)Rs) in the brain. CB(1)R is a seven-transmembrane domain. G(i/o)-protein coupled receptors, and is expressed throughout the central nervous system including the hippocampus, cerebellum, striatum and cerebral cortex. Endogenous ligands for CB(1)R (endocannabinoids) are lipid in nature, and anandamide and 2-arachidonoylglycerol (2-AG) are considered to be the two major endocannabinoids. Endocannabinoids are known to function as retrograde messengers at synapses. Endocannabinoids are released from postsynaptic neurons in activity-dependent manners, and retrogradely activate presynaptic CB(1)Rs, resulting in short-term or long-term suppression of synaptic transmission. Endocannabinoid-mediated retrograde signaling is observed at various brain regions and considered as a general mechanism of synaptic modulation in the brain. Endocannabinoid release is triggered by postsynaptic Ca2+ elevation or activation of G(q/11)-protein coupled receptors. Recent studies have demonstrated that 2-AG mediates retrograde signaling at synapses in the brain. Endocannabinoid-mediated retrograde signaling is involved in long-term synaptic plasticity in several brain regions. At behavioral level, endocannabinoid signaling is known to be involved in hippocampus-, amygdala- and cerebellum-dependent learning and memory.
吸食大麻会通过大脑中的1型大麻素受体（CB(1)Rs）引发各种精神活性效应。CB(1)R是一种七跨膜结构域、与G(i/o)蛋白偶联的受体，在包括海马体、小脑、纹状体和大脑皮层在内的整个中枢神经系统中均有表达。CB(1)R的内源性配体（内源性大麻素）本质上是脂质，花生四烯乙醇胺和2-花生四烯酸甘油酯（2-AG）被认为是两种主要的内源性大麻素。已知内源性大麻素在突触处作为逆行信使发挥作用。内源性大麻素以活动依赖的方式从突触后神经元释放，并逆行激活突触前CB(1)Rs，导致突触传递的短期或长期抑制。内源性大麻素介导的逆行信号在大脑的各个区域都能观察到，被认为是大脑中突触调制的一种普遍机制。内源性大麻素的释放由突触后Ca2+升高或G(q/11)蛋白偶联受体的激活触发。最近的研究表明，2-AG在大脑突触处介导逆行信号。内源性大麻素介导的逆行信号参与了几个脑区的长期突触可塑性。在行为水平上，已知内源性大麻素信号参与海马体、杏仁核和小脑依赖的学习和记忆。
