Dose-dependent impairment of inhibitory avoidance retention in rats by immediate post-training infusion of a mitogen-activated protein kinase kinase inhibitor into cortical structures

Mitogen-activated protein kinase (MAPK) is a serine/threonine protein kinas e abundantly expressed in postmitotic neurons of the developed nervous syst em. MAPK is activated in and required for both the induction of long-term p otentiation (LTP) in hippocampal slices and the acquisition of fear conditi oning training in rats. The present work was performed in order to test the effect of the specific inhibitor of MAPK kinase (MAPKK), PD 098059, on ret ention of a step-down inhibitory avoidance (IA). Adult male Wistar rats wer e bilaterally injected (0.5 mu l/side) with PD 098059 (at 0.5, 5, or 50 mu M) or vehicle into the entorhinal cortex or into the parietal cortex immedi ately after IA training using a 0.4 mA footshock. Retention testing was car ried out 24 h after training. PD 098059 impaired retention when injected in to the entorhinal cortex at the dose of 50 mu M, but not at the doses of 5 or 0.5 mu M. When infused into the parietal cortex, PD 098059 was amnestic at the doses of 5 and 50 mu M. The drug had no effect when infused at the h ighest dose in either structure 6 h after training. Our results suggest tha t the MAPKK inhibitor impairs IA retention memory in a dose-dependent manne r when injected immediately after training into entorhinal cortex or pariet al cortex. The effective dose is variable according to the neocortical stru cture studied. (C) 1999 Elsevier Science B.V. All rights reserved.