GABA(B)-RECEPTOR ACTIVATION ALTERS THE FIRING PATTERN OF DOPAMINE NEURONS IN THE RAT SUBSTANTIA-NIGRA
GABA(B)-RECEPTOR ACTIVATION ALTERS THE FIRING PATTERN OF DOPAMINE NEURONS IN THE RAT SUBSTANTIA-NIGRA
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DOI：
10.1002/syn.890150308
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发表时间：
1993-11-01
期刊：
影响因子：
2.3
通讯作者：
NISSBRANDT, H
中科院分区：
文献类型：
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作者：
ENGBERG, G;KLINGPETERSEN, T;NISSBRANDT, H
以往的电生理实验强调了放电模式对中脑多巴胺（DA）神经元功能的重要性。在这方面，兴奋性氨基酸受体似乎构成了一个重要的调节控制机制。本研究应用细胞外记录技术，探讨了GABA（B）受体激活对大鼠黑质DA能神经元放电特性的影响。GABA（B）受体激动剂巴氯芬（1-16 mg/kg）的静脉给药与放电模式的剂量依赖性规则化相关，伴随着猝发放电的减少。在较高剂量（16-32 mg/kg）下，DA神经元的放电率呈剂量依赖性降低。此外，巴氯芬的微离子电渗应用程序规范的黑质DA神经元的放电模式，包括减少突发放电。GABA（B）受体拮抗剂CGP 35348（200 mg/kg，静脉注射）可拮抗全身性巴氯芬给药引起的放电模式的规则化和放电率的抑制。GABA（A）受体激动剂蝇蕈醇对DA神经元的放电特性产生的影响与巴氯芬后观察到的相反，即，伴随着规律性降低的发射率的增加。NMDA受体拮抗剂MK 801（0.4- 3.2mg/kg，i. v.）产生了一个温和的，剂量依赖性的增加，在黑质DA神经元的放电率，以及稍微正规化的放电模式。用MK 801（3.2mg/kg，静脉内，3-10 min）既不促进也不阻止巴氯芬产生的黑质DA神经元放电模式的规则化或放电速率的抑制。目前的结果清楚地表明，GABA（B）-受体可以改变黑质DA神经元的放电模式，从而抵消了先前描述的谷氨酸诱导这些神经元爆发放电活动的能力。(c)1993 Wiley-Liss，Inc.
Previous electrophysiological experiments have emphasized the importance of the firing pattern for the functioning of midbrain dopamine (DA) neurons. In this regard, excitatory amino acid receptors appear to constitute an important modulatory control mechanism. In the present study, extracellular recording techniques were used to investigate the significance of GABA(B)-receptor activation for the firing properties of DA neurons in the substantia nigra (SN) in the rat. Intravenous administration of the GABA(B)-receptor agonist baclofen (1-16 mg/kg) was associated with a dose-dependent regularisation of the firing pattern, concomitant with a reduction in burst firing. At higher doses (16-32 mg/kg), the firing rate of the DA neurons was dose-dependently decreased. Also, microiontophoretic application of baclofen regularized the firing pattern of nigral DA neurons, including a reduction of burst firing. Both the regularisation of the firing pattern and inhibition of firing rate produced by systemic baclofen administration was antagonized by the GABA(B)-receptor antagonist CGP 35348 (200 mg/kg, i.v.). The GABA(A)-receptor agonist muscimol produced effects on the firing properties of DA neurons that were opposite to those observed following baclofen, i.e., an increase in firing rate accompanied by a decreased regularity. The NMDA receptor antagonist MK 801 (0.4-3.2 mg/kg, i.v.) produced a moderate, dose-dependent increase in the firing rate of the nigral DA neurons as well as a slightly regularized firing pattern. Pretreatment with MK 801 (3.2 mg/kg, i.v., 3-10 min) did neither promote nor prevent the regularisation of the firing pattern or inhibition of firing rate on the nigral DA neurons produced by baclofen. The present results clearly show that GABA(B)-receptors can alter the firing pattern of nigral DA neurons, hereby counterbalancing the previously described ability of glutamate to induce burst firing activity on these neurons. (c) 1993 Wiley-Liss, Inc.