Possible involvement of the CA1 GABAergic system on harmaline induced memory consolidation deficit

Abstract

Activation of the GABA receptors inhibit learning and memory processes. The current research was designed to examine the role of dorsal hippocampal (CA1) GABA receptors on harmaline induced memory consolidation deficit in mice. For this purpose, the effects induced by the GABA antagonist phaclofen and the GABA agonist baclofen on memory consolidation were assessed by using the step-down inhibitory avoidance task. Furthermore, the possible involvement of harmaline on GABA receptor's effects was also assessed through using the same behavioral procedure. In a first dose response experiments, post-training intra-CA1 injections of phaclofen did not change while baclofen (0.1μg/mouse) impaired animals' performance in this task, suggesting a modulation of storage of information. Moreover, Post-training intra-peritoneal (i.p.) infusion of harmaline (2 and 5mg/kg) also decreased memory consolidation. Interestingly, phaclofen at the sub-threshold dose (0.001μg/mouse, intra-CA1), successfully antagonized the deficits on memory consolidation induced by the highest doses of harmaline (2 and 4mg/kg, i.p.). On the other hand, non significant dose of baclofenc (0.001μg/mouse, intra-CA1) potentiated impairment of memory consolidation induced by harmaline (2mg/kg, i.p.). In addition in all experiments, locomotor activity did not alter significantly. These results indicate a) that the CA1 GABA receptors are involved in memory consolidation b) that harmaline interact with the CA1 GABA receptors in modulation of memory consolidation.