GABAB受体激动剂巴氯芬对大鼠中脑导水管周围灰质兴奋性及抑制性突触的作用

Effect of GABA_B receptor agonist baclofen on excitatory and inhibitory synapses of ventrolateral periaqueductal gray in rats

目的研究大鼠中脑导水管周围灰质(periaqueductal gray, PAG)内饱和及非饱和浓度的GABA_B受体激动剂对兴奋性突触及抑制性突触作用的异同。方法利用全细胞膜片钳记录方法在成年大鼠PAG的急性横切薄片记录其腹外侧区神经元。结果饱和浓度的GABA_B受体激动剂巴氯芬(baclofen,5μmol·L^(-1))对上述两类突触的抑制效果无统计学差异,而非饱和浓度的巴氯芬(0.1μmol·L^(-1))对上述两类突触的作用有差异,0.1μmol·L^(-1)巴氯芬对抑制性突触的抑制效应明显大于其对兴奋性突触的抑制。与之相对应,0.1μmol·L^(-1)巴氯芬对单个PAG神经元的兴奋性显示增加作用,而非抑制作用。结论饱和浓度的GABA_B受体激动剂巴氯芬抑制两类突触的比率无差别,而非饱和浓度的巴氯芬对抑制性突触的抑制作用比其对兴奋性突触的抑制效率高,此结果可能解释了PAG注射不同浓度巴氯芬引起不同行为学反应的原因。

Aim To investigate the possible difference between glutamatergic synapses and GABAergic synapses in the ventrolateral periaqueductal gray(vlPAG)when GABAB receptor agonist is at nonsaturating concentration or saturating concentration.Methods We employed whole cell patch-clamp recordings on acute PAG slices from adult rats.Results Glutamatergic synapses were less sensitive to baclofen,a putative GABAB receptor agonist,than that of GABAergic synapses,but only at nonsaturating concentration(0.1μmol·L^-1).On the contrary,saturating concentration of baclofen(5μmol·L^-1)inhibited both glutamatergic and GABAergic synapses to a similar ratio.Accordingly,low concentration of baclofen increased,while high concentration decreased the excitability of postsynaptic vlPAG neurons.Conclusions The overall action of baclofen in vlPAG depends on its concentrations.Since vlPAG plays an important role in reducing pain modulation system,the different concentrations of GABA may induce its varying actions on modulation.