Effect of bilateral destruction of the subretrofacial area on receptor mechanisms of neuroprotective effect of GABAergic agents

Abstract

Both GBA A (muscimol, gaboxadol, and isonipecotate) and GABA B (baclofen) receptor agonists produce marked neuroprotective effect during total brain ischemia. The antagonists of GABA^ receptors bicuculline and picrotoxin attenuate the effect of muscimol, and the GABA a receptor antagonists hydroxysaclofen and aminovaleriate decrease the effect of baclofen. The GABAergic substances protect the brain via GABA receptors of both types. The effect of the GABA agonists is central in nature. Key Words: GABA receptors; neuroprotectors; brain ischemia,/-Aminobutyric acid (GABA) is the main inhibiting transmitter in the brain. Its effect is realized via different signal-transducing systems: 1) ionotropic GABA A receptors, which are C1--channels that hyperpolarize cells due to inflow of chloride ions; and 2) metabotropic GABA B receptors, which open K § and close Ca 2 § channels via Gi/~ proteins and inhibit adenylyl cyclase [5,6,13]. Recently, GABA B receptors were cloned [8]. The agonist of GABA s receptors baclofen has a pronounced neuroprotective effect (NPE) during brain ischemia in the rodents [2,3,7,9]. The data on muscimol, an agonist of GABA A receptors, are equivocal [7,10,12]. The effects of GABA receptor antagonists were studied only for NPE of baclofen [7].Our aim was to elucidate the receptor mechanisms of NPE of GABA-ergie agents using two independent methods: 1) comparison of activity of selective agonists of different GABA receptors and 2) blockade of the effects by selective antagonists [5,6,13]. MATERIALS AND METHODSThe study was carried out on 372 CBA and C57B1 mice of both sexes weighing 18-25 g. The following