Niittykoski M, Ruotsalainen S, Haapalinna A, Larson J, Sirviö J
A. I. Virtanen Institute, University of Kuopio, Finland.
Neuroscience. 1999 Apr;90(1):95-105. doi: 10.1016/s0306-4522(98)00447-3.
The aim of this study was to characterize the modulation of synaptic transmission in the glutamatergic corticostriatal pathway by cholinergic and adrenergic receptors. In coronal slices of mouse brain, negative-going field potentials were recorded in the dorsal striatum in response to stimulation of the overlying white matter, and their susceptibility to various pharmacological manipulations was studied. The responses were mediated by alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors, since they were augmented by aniracetam (0.5-1.5 mM), a positive modulator of AMPA-type glutamate receptors, and blocked by 6-cyano-7-nitroquinoxaline-2,3-dione (> or = 10 microM), a selective antagonist of AMPA receptors. Carbachol (10 microM), a muscarinic agonist, reduced the size of responses and abolished paired-pulse depression; these effects being consistent with previous studies indicating that muscarinic activation inhibits release of glutamate in the corticostriatal pathway. Muscarinic antagonists could block the effect of carbachol. Their rank order was: 10 microM scopolamine (a non-selective muscarinic antagonist) > or = 1 microM 4-diphenylacetoxy-N-methyl-piperidine (M3/M1 antagonist)>1 microM pirenzepine (M1 antagonist)>10 microM methoctramine (M2 antagonist). McN-A-343 (1-10 microM), an M1 muscarinic agonist, was ineffective in this preparation. In contrast, isoproterenol (10-30 microM), a beta-adrenergic agonist, slightly increased the synaptic responses, but it did not affect paired-pulse depression. None of alpha-adrenergic agents (30 nM-1.0 microM dexmedetomidine, an alpha2-adrenergic agonist, 0.3 microM atipamezole, an alpha2-adrenergic antagonist or 30 microM phenylephrine, an alpha1-adrenergic agonist) influenced the size of the responses; neither did these drugs alter paired-pulse depression. These results indicate that the activation of striatal M3-like muscarinic receptors and beta-adrenoceptors, but not M2-like muscarinic receptors and alpha-adrenoceptors, modulates directly corticostriatal glutamatergic neurotransmission.
本研究的目的是描述胆碱能和肾上腺素能受体对谷氨酸能皮质纹状体通路中突触传递的调节作用。在小鼠脑冠状切片中，刺激覆盖的白质时记录背侧纹状体中的负向场电位，并研究其对各种药理学操作的敏感性。这些反应由α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）型谷氨酸受体介导，因为它们被AMPA型谷氨酸受体的正向调节剂茴拉西坦（0.5 - 1.5 mM）增强，并被AMPA受体的选择性拮抗剂6-氰基-7-硝基喹喔啉-2,3-二酮（≥10 μM）阻断。毒蕈碱激动剂卡巴胆碱（10 μM）减小了反应幅度并消除了双脉冲抑制；这些效应与先前的研究一致，表明毒蕈碱激活抑制皮质纹状体通路中谷氨酸的释放。毒蕈碱拮抗剂可阻断卡巴胆碱的作用。其顺序为：10 μM东莨菪碱（非选择性毒蕈碱拮抗剂）≥1 μM 4-二苯基乙酰氧基-N-甲基哌啶（M3/M1拮抗剂）>1 μM哌仑西平（M1拮抗剂）>10 μM甲溴东莨菪碱（M2拮抗剂）。M1毒蕈碱激动剂 McN-A-343（1 - 10 μM）在此制剂中无效。相反，β-肾上腺素能激动剂异丙肾上腺素（10 - 30 μM）略微增加了突触反应，但不影响双脉冲抑制。α-肾上腺素能药物（30 nM - 1.0 μM右美托咪定，α2-肾上腺素能激动剂；0.3 μM阿替美唑，α2-肾上腺素能拮抗剂；或30 μM去氧肾上腺素，α1-肾上腺素能激动剂）均未影响反应幅度；这些药物也未改变双脉冲抑制。这些结果表明，纹状体M3样毒蕈碱受体和β-肾上腺素能受体的激活直接调节皮质纹状体谷氨酸能神经传递，而M2样毒蕈碱受体和α-肾上腺素能受体则不然。
