Role of GABAB receptors in GABA and baclofen-induced inhibition of adult rat cerebellar interpositus nucleus neurons in vitro
Role of GABAB receptors in GABA and baclofen-induced inhibition of adult rat cerebellar interpositus nucleus neurons in vitro
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DOI：
10.1016/j.brainresbull.2005.07.004
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发表时间：
2005-10-30
影响因子：
3.8
通讯作者：
Wang, JJ
中科院分区：
文献类型：
--
作者：
Chen, K;Li, HZ;Wang, JJ
以往的研究表明，选择性GABA（B）受体激动剂巴氯芬或小脑皮质浦肯野细胞释放的内源性GABA不能激活成年大鼠小脑深核神经元的突触后GABA（B）受体，尽管已证实该受体存在于小脑深核。本研究制备了成年大鼠小脑脑片，观察了GABA、巴氯芬和蝇蕈醇（选择性GABA（A）受体激动剂）对小脑中间核（IN）神经元的作用。用GABA（10-1000 μ M）、巴氯芬（1-30 μ M）和蝇蕈醇（1-100 μ M）分别灌流脑片，对IN神经元产生剂量依赖性抑制反应（n = 39，62和5.0），这种抑制反应不被低Ca ~（2+）/高Mg ~（2+）介质（n = 5，6和6）阻断，支持这些GABA能激动剂的直接突触后作用。选择性GABA（B）受体拮抗剂CGP 35348和选择性GABA（A）受体拮抗剂荷包牡丹碱均能部分阻断IN神经元对GABA的抑制反应（n = 14和11），提示GABA所指示的抑制成分可能包含GABA（B）受体介导的抑制成分和GABA（A）受体介导的抑制成分。进一步的实验表明，不仅蝇蕈醇（n = 50），巴氯芬（n = 62）抑制IN-细胞。活动CGP 35348（n = 62）选择性地阻断了Bacillin诱导的抑制作用，而荷包牡丹碱（n = 8）不阻断Bacillin诱导的抑制作用，而荷包牡丹碱（n =8）选择性地拮抗蝇蕈醇诱导的抑制作用，而CGP 35348（n=9）不拮抗Bacillin诱导的抑制作用。这些结果表明，神经元中的GABA（B）受体不仅可以被GABA激活，而且也可以被巴氯芬激活，这表明除了GABA（A）受体外，GABA（B）受体1也可能参与介导GABA对成年大鼠小脑IN神经元的抑制作用。(c)2005年爱思唯尔公司All rights reserved.
Previous studies suggested that the postsynaptic, GABA(B) receptors of deep cerebellar nuclear neurons of adult rats were not activated by selective GABA(B) receptor agonist baclofen or endogenous GABA released by cerebellar cortical Purkinje cells, although the receptors have been demonstrated to exist in the deep cerebellar nuclei. In this study, cerebellar slices of adult rats were prepared for testing effects of GABA, baclofen and muscimol (selective GABA(A) receptor agonist) on cerebellar interpositus nucleus (IN) neurons. Perfusing, slices with GABA (10-1000 mu M), baclofen (1-30 mu M) and muscimol (1-100 mu M) respectively produced a dose-dependent inhibitory response on the IN neurons (n = 39, 62 and 5.0),which was not blocked by low-Ca2+/high-Mg2+ medium (n = 5, 6 and 6), supporting a direct postsynaptic action of these GABAergic agonists. Moreover, both selective GABA(B) receptor antagonist CGP35348 and selective GABA(A) receptor antagonist bicuculline were capable of partially blocking the inhibitory response of IN neurons to GABA (n = 14 and 11), suggesting that the GABA-indicated inhibition component may contain two components, a GABA(B) receptors-mediate and a GABA(A) receptors-mediated one. Further experiments revealed that not only muscimol (n 50) but also baclofen (n = 62) suppressed IN-cells,. activity. The baclofen-induced inhibition was selectively blocked by CGP35348 (n = 62) but not by bicuculline (n = 8) whereas the muscimol-induced inhibition was selectively antagonised by bicuculline (n=8) instead of CGP35348 (n=9) These results indicate that GABA(B) receptors in the neurons can be activated not only by GABA but also by baclofen suggesting that besides GABA(A) receptors, GABA(B) receptors 1, may also be involved in mediating the inhibitory effect of GABA on cerebellar IN neurons of adult rats. (c) 2005 Elsevier Inc. All rights reserved.