Different time course for the memory facilitating effect of bicuculline in hippocampus, entorhinal cortex, and posterior parietal cortex of rats

Several lines of evidence indicate that gamma-aminobutyric acid (GABA) type A (GABA(A)) receptors regulate memory consolidation. Here we studied the effect on consolidation of the selective antagonist of GABA(A) receptors, bicuculline, given into several regions of the cortex at different times after one-trial step-down inhibitory avoidance (0.5 mA, 2-s footshock). Rats were bilaterally implanted with cannulae aimed at the CA1 region of the dorsal hippocampus, entorhinal cortex or posterior parietal cortex, three areas known to be involved in the memory consolidation of this task. At different times after training, bicuculline (0.5 mug/side) was infused into the above mentioned structures. Bicuculline increased memory retention when administered either immediately or 1.5 h after training into CA1, and both immediately and 3 h after training in the entorhinal or parietal cortex. Thus, in agreement with previous findings using other drugs, the response was biphasic in these latter structures. This suggests that GABAergic mechanisms normally downregulate, memory processing by inhibiting on-going activities necessary for consolidation at the times in which bicuculline was effective in each structure. Based on previous findings, in the hippocampus, such activity involves a number of receptors and signaling pathways in the first 1.5 h after training. In the entorhinal and parietal cortex memory-related activities include the participation of protein kinase A and extracellularly regulated kinase (ERK) twice, right after training and then again 3 h later. (C) 2004 Elsevier Inc. All rights reserved.