Effects of post-training infusions of a mitogen-activated protein kinase kinase inhibitor into the hippocampus or entorhinal cortex on short- and long-term retention of inhibitory avoidance

We recently demonstrated the time-dependent impairment of long-term retenti on of a step-down inhibitory avoidance task in rats induced by post-trainin g infusion of the specific MAPKK (mitogen-activated protein kinase kinase) inhibitor PD 098059 into the hipoccampus (HIP), amygdala (ARTY), entorhinal cortex (EC) and posterior parietal cortex (PPC). Here we investigate the r ole of the MAPK cascade in the HIP and the EC on both short- and long-term retention of inhibitory avoidance in rats, using three different doses of t he MAPKK inhibitor PD 098059. Adult male Wistar rats were trained and teste d in inhibitory avoidance and given an infusion of PD 098059 (0.5, 5.0 or 5 0.0 mu M) at 0, 30, 90, 120, 180, 270 or 360 min after training. A retentio n test session was carried out at 90, 180 or 270 min after training (short- term memory, STM) and/or 24 h after training (long-term memory, LTM). When infused into the HIP at 0 min, but not at 30, 90, 120 or 180 min after trai ning, PD 098059 impaired STM. Intrahippocampal PD 098059 impaired LTM when infused at 180 min, but not at 0, 30, 90, 120 or 270 min after training. Wh en infused into the EC, PD 098059 enhanced STM when given at 0 min after tr aining and had no effect when given at 30, 90, 120 or 180 min after trainin g. In this structure, PD 098059 impaired LTM when given at 180 or 270 min, but not at 30, 90, 120 or 360 min after training. All effects were dose-dep endent. These findings indicate that the MAPK cascade in the HIP and EC is differentially involved in short- and long-term retention of inhibitory avo idance in rats. (C) 1999 Lippincott Williams & Wilkins.