Salt T E, Eaton S A
Department of Visual Science, Institute of Ophthalmology, London, U.K.
Neuropharmacology. 1995 Aug;34(8):1043-51. doi: 10.1016/0028-3908(95)00052-8.
Several different types of metabotropic excitatory amino acid receptors (mGluRs) are present in the thalamus. We have previously shown that the agonists L-AP4 and CCG-I can have apparently presynaptic effects on GABAergic inhibitory transmission in the thalamus. In this study we attempted to characterize the different receptor types which may mediate these effects and the known post-synaptic excitatory actions of 1S,3R-ACPD in the ventrobasal thalamus, by using a number of agonists with different spectra of activity at the various mGluRs. Inhibitory responses in ventrobasal thalamic neurones of urethane-anaesthetized rats were evoked by air-jet stimuli to the vibrissae and extracellular recording methods were used to reveal inhibitory responses as an inhibition of excitatory responses in a condition-test paradigm. The Group II and Group III mGluR agonists L-AP4, CCG-I, DCG-IV, 1S,3R-ACPD and S-4C3HPG, applied in the vicinity of the recording site by iontophoresis, were found to reduce inhibitions revealed by the condition-test paradigm (by 67, 75, 50, 43 and 77% from control inhibitions, respectively). The endogenous mGluR agonist L-serine-O-phosphate (L-SOP) was found to have similar, although weaker, actions (31% reduction of inhibition), while the Group I agonist 3,5-DHPG had little effect in this test (9% reduction of inhibition). In contrast, both 3,5-DHPG and 1S,3R-ACPD had direct excitatory actions on VB neurones, and these could be antagonized by 4CPG. The effects of CCG-I in the condition-test paradigm could be antagonized by the antagonists MCCG, MCPG, but not MAP4.(ABSTRACT TRUNCATED AT 250 WORDS)
丘脑存在几种不同类型的代谢型兴奋性氨基酸受体(mGluRs)。我们之前已经表明,激动剂L-AP4和CCG-I对丘脑的GABA能抑制性传递可能具有明显的突触前效应。在本研究中,我们试图通过使用一系列在各种mGluRs上具有不同活性谱的激动剂,来确定可能介导这些效应的不同受体类型,以及1S,3R-ACPD在腹侧基底丘脑中已知的突触后兴奋性作用。通过向大鼠触须施加喷气刺激,诱发经乌拉坦麻醉的大鼠腹侧基底丘脑神经元的抑制反应,并采用细胞外记录方法,在条件-测试范式中,将抑制反应显示为对兴奋性反应的抑制。通过离子电泳将II组和III组mGluR激动剂L-AP4、CCG-I、DCG-IV、1S,3R-ACPD和S-4C3HPG应用于记录部位附近,发现它们可减少条件-测试范式显示的抑制作用(分别比对照抑制作用降低67%、75%、50%、43%和77%)。发现内源性mGluR激动剂L-丝氨酸-O-磷酸(L-SOP)具有类似但较弱的作用(抑制作用降低31%),而I组激动剂3,5-DHPG在该测试中几乎没有作用(抑制作用降低9%)。相反,3,5-DHPG和1S,3R-ACPD对VB神经元均有直接兴奋性作用,且这些作用可被4CPG拮抗。CCG-I在条件-测试范式中的作用可被拮抗剂MCCG、MCPG拮抗,但不能被MAP4拮抗。(摘要截短于250字)