Effects of intrahippocampal GABAB receptor antagonist treatment on the behavioral long-term potentiation and Y-maze learning performance

GABA(B) receptor is present at pre- and post-synaptic sites and participates in many brain functions including cognition, reward and anxiety. Although a lot of research has shown that activation or blockade of GABAB receptor may produce different even opposing effects on long-term potentiation (LTP) and cognitive function, there is little information available concerning the effect of GABA(B) receptor on behavioral LTP, a learning-induced LTP model. Herein, we firstly examined the effects of 2-OH saclofen, a GABA(B) receptor antagonist, on the induction of behavioral LTP and Y-maze learning performance. In addition, GABAB receptor has been reported to be present on cholinergic terminals and to regulate the ACh release. Therefore, we also investigated the effect of 2-OH saclofen on the impairments in behavioral LTP and cognitive function induced by scopolamine, an acetylcholine receptor antagonist. We found that intrahippocampal application of 2-OH saclofen could significantly enhance the population spike (PS) amplitude with a dose-response relationship, and 20 mu M 2-OH saclofen evidently facilitated the formation of behavioral LTP in the perforant pathway to the dentate gyrus (PP-DG) and led to an obvious improvement in maze learning performance. Furthermore, intrahippocampal 20 mu M 2-OH saclofen administration could markedly reverse the scopolamine-induced impairments in behavioral LTP and maze performance. Our data demonstrate that blockade of GABA(B) receptor displays a facilitatory role in the induction of behavioral LTP and maze learning task, and the antagonist of GABA(B) receptor seems to exert the potentially therapeutic value in the cognitive defect induced by cholinergic dysfunction. (C) 2014 Elsevier Inc. All rights reserved.