Melis Miriam, Muntoni Anna Lisa, Pistis Marco
B.B. Brodie Department of Neuroscience, University of Cagliari Monserrato, Italy.
Front Pharmacol. 2012 Feb 2;3:7. doi: 10.3389/fphar.2012.00007. eCollection 2012.
Endocannabinoids serve as retrograde signaling molecules at many synapses within the CNS, particularly GABAergic and glutamatergic synapses. Synapses onto midbrain dopamine (DA) neurons in the ventral tegmental area (VTA) make no exception to this rule. In fact, the effects of cannabinoids on dopamine transmission as well as DA-related behaviors are generally exerted through the modulation of inhibitory and excitatory afferents impinging onto DA neurons. Endocannabinoids, by regulating different forms of synaptic plasticity in the VTA, provide a critical modulation of the DA neuron output and, ultimately, of the systems driving and regulating motivated behaviors. Because DA cells exhibit diverse states of activity, which crucially depend on their intrinsic properties and afferent drive, the understanding of the role played by endocannabinoids in synaptic modulations is critical for their overall functions. Particularly, endocannabinoids by selectively inhibiting afferent activity may alter the functional states of DA neurons and potentiate the responsiveness of the reward system to phasic DA.
内源性大麻素在中枢神经系统（CNS）的许多突触中充当逆行信号分子，尤其是在γ-氨基丁酸（GABA）能和谷氨酸能突触中。投射到腹侧被盖区（VTA）中脑多巴胺（DA）神经元上的突触也不例外。事实上，大麻素对多巴胺传递以及与DA相关行为的影响通常是通过调节作用于DA神经元的抑制性和兴奋性传入神经来实现的。内源性大麻素通过调节VTA中不同形式的突触可塑性，对DA神经元输出以及最终对驱动和调节动机行为的系统进行关键调节。由于DA细胞表现出多种活动状态，这关键取决于它们的内在特性和传入驱动，因此了解内源性大麻素在突触调制中所起的作用对于它们的整体功能至关重要。特别是，内源性大麻素通过选择性抑制传入活动，可能会改变DA神经元的功能状态，并增强奖励系统对阶段性DA的反应性。
