Mott D D, Bragdon A C, Lewis D V, Wilson W A
Department of Pharmacology, Duke University Medical Center, Durham, North Carolina.
J Pharmacol Exp Ther. 1989 Jun;249(3):721-5.
Effects of the gamma-aminobutyric acidB (GABAB) agonist baclofen on evoked responses and recurrent inhibition in the dentate gyrus were examined in rat hippocampal slices. Granule cell firing was induced by perforant path stimulation; recurrent inhibition was induced by pairing the perforant path stimulus with a preceding mossy fiber stimulus and was mediated through GABAA receptors. Whereas (+/-)-baclofen (10 microM) suppressed the perforant path-evoked population spike only about 20%, it suppressed recurrent inhibition about 84% and converted the perforant path-evoked response to an epileptiform response with multiple population spikes. These effects were concentration-dependent (estimated EC50 values for (+/-)-baclofen were 0.6 microM for suppression of recurrent inhibition and 1.0 microM for induction of multiple population spikes) and stereoselective for (-)-baclofen. Baclofen had no effect on GABAA-mediated inhibiton induced by focal application of GABA to the granule cells. These results suggest that baclofen suppressed recurrent inhibition through an action mediated by GABAB receptors on inhibitory interneurons. They also suggest the net effect of baclofen was proepileptic because its disinhibitory effect was substantially greater than its suppressive effect on synaptic excitation.
在大鼠海马切片中，研究了γ-氨基丁酸B（GABAB）激动剂巴氯芬对齿状回诱发反应和反馈抑制的影响。通过穿通通路刺激诱导颗粒细胞放电；通过将穿通通路刺激与先前的苔藓纤维刺激配对来诱导反馈抑制，该抑制由GABAA受体介导。虽然（±）-巴氯芬（10μM）仅使穿通通路诱发的群体峰电位抑制约20%，但它使反馈抑制抑制约84%，并将穿通通路诱发的反应转变为具有多个群体峰电位的癫痫样反应。这些效应呈浓度依赖性（（±）-巴氯芬抑制反馈抑制的估计EC50值为0.6μM，诱导多个群体峰电位的EC50值为1.0μM），并且对（-）-巴氯芬具有立体选择性。巴氯芬对局灶性应用GABA于颗粒细胞所诱导的GABAA介导的抑制没有影响。这些结果表明，巴氯芬通过GABAB受体对抑制性中间神经元的作用抑制反馈抑制。它们还表明，巴氯芬的净效应是促癫痫的，因为其去抑制作用远大于其对突触兴奋的抑制作用。
