Section of Central Nervous System Pharmacology, Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanità, Rome, Italy.
J Neurochem. 2011 Jan;116(2):273-80. doi: 10.1111/j.1471-4159.2010.07101.x. Epub 2010 Dec 2.
An interaction between adenosine A(2A) receptors (A(2A) Rs) and cannabinoid CB(1) receptors (CB(1) Rs) has been consistently reported to occur in the striatum, although the precise mechanisms are not completely understood. As both receptors control striatal glutamatergic transmission, we now probed the putative interaction between pre-synaptic CB(1) R and A(2A) R in the striatum. In extracellular field potentials recordings in corticostriatal slices from Wistar rats, A(2A) R activation by CGS21680 inhibited CB(1) R-mediated effects (depression of synaptic response and increase in paired-pulse facilitation). Moreover, in superfused rat striatal nerve terminals, A(2A) R activation prevented, while A(2A) R inhibition facilitated, the CB(1) R-mediated inhibition of 4-aminopyridine-evoked glutamate release. In summary, the present study provides converging neurochemical and electrophysiological support for the occurrence of a tight control of CB(1) R function by A(2A) Rs in glutamatergic terminals of the striatum. In view of the key role of glutamate to trigger the recruitment of striatal circuits, this pre-synaptic interaction between CB(1) R and A(2A) R may be of relevance for the pathogenesis and the treatment of neuropsychiatric disorders affecting the basal ganglia.
腺嘌呤 A(2A) 受体 (A(2A) Rs) 和大麻素 CB(1) 受体 (CB(1) Rs) 之间的相互作用在纹状体中一直被报道，尽管确切的机制尚不完全清楚。由于这两种受体都控制纹状体中的谷氨酸能传递，我们现在探究了纹状体中预突触 CB(1) R 和 A(2A) R 之间的潜在相互作用。在来自 Wistar 大鼠的皮质纹状体切片的细胞外场电位记录中，CGS21680 激活 A(2A) R 抑制了 CB(1) R 介导的作用（抑制突触反应和增加成对脉冲易化）。此外，在超流大鼠纹状体神经末梢中，A(2A) R 激活阻止，而 A(2A) R 抑制促进了 CB(1) R 介导的对 4-氨基吡啶诱导的谷氨酸释放的抑制。总之，本研究为纹状体谷氨酸能末梢中 A(2A) Rs 对 CB(1) R 功能的紧密控制提供了神经化学和电生理学的支持。鉴于谷氨酸在触发纹状体回路募集中的关键作用，这种 CB(1) R 和 A(2A) R 之间的突触前相互作用可能与影响基底神经节的神经精神疾病的发病机制和治疗有关。
