We recently demonstrated the time-dependent impairment of long-term retention of a step-down inhi... more We recently demonstrated the time-dependent impairment of long-term retention of a step-down inhibitory avoidance task in rats induced by post-training infusion of the specific MAPKK (mitogen-activated protein kinase kinase) inhibitor PD 098059 into the hippocampus (HIP), amygdala (AMY), entorhinal cortex (EC) and posterior parietal cortex (PPC). Here we investigate the role 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 the MAPKK inhibitor PD 098059. Adult male Wistar rats were trained and tested in inhibitory avoidance and given an infusion of PD 098059 (0.5, 5.0 or 50.0 microM) at 0, 30, 90, 120, 180, 270 or 360 min after training. A retention 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 training, 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. When infused into the EC, PD 098059 enhanced STM when given at 0 min after training and had no effect when given at 30, 90, 120 or 180 min after training. 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-dependent. These findings indicate that the MAPK cascade in the HIP and EC is differentially involved in short- and long-term retention of inhibitory avoidance in rats.
Rats received, through bilaterally implanted indwelling cannulae, 0.5 microliter infusions of 6-c... more Rats received, through bilaterally implanted indwelling cannulae, 0.5 microliter infusions of 6-cyano-7-nitroquinoxaline2,3-dione (CNQX) (0.5 microgram), D-2-amino-5-phophono pentanoic acid (AP5) (5.0 micrograms), muscimol (0.5 microgram), scopolamine (2.0 micrograms), SCH23390 (2.5 micrograms), saline or a vehicle into the CA1 region of the hippocampus, or into the antero-lateral prefrontal (PRE), posterior parietal (PP) and entorhinal cortex (EC). The infusions were given 6 min prior to one-trial step-down inhibitory avoidance training in order to measure their effect on working memory (WM), or immediately post-training in order to measure their effect on short-term (STM) and long-term memory (LTM), 1.5 and 24 h later, respectively. WM was inhibited by CNQX or muscimol given into any of the cortical areas, by SCH23390 given into CA1, PRE or PP, and by scopolamine given into PRE or EC. STM was unaffected by any of the treatments given into PRE, and was inhibited by CNQX or muscimol given into CA1, PP and EC and by scopolamine given into PP, and enhanced by SCH given into CA1. LTM was inhibited by CNQX, muscimol, scopolamine or SCH23390 given into PRE, by scopolamine given into PP, by SCH23390 given into the entorhinal cortex, and by AP5, CNQX, muscimol or scopolamine given into CA1. The results indicate a differential involvement of the various neurotransmitter systems in the three types of memory in the various brain areas, and a separation of the mechanisms and of the regions involved in each. In addition, some of the findings suggested links between WM and LTM processing in PRE, between WM and STM processing in EC and PP, and between all three types of memory in CA1.
We recently demonstrated the time-dependent impairment of long-term retention of a step-down inhi... more We recently demonstrated the time-dependent impairment of long-term retention of a step-down inhibitory avoidance task in rats induced by post-training infusion of the specific MAPKK (mitogen-activated protein kinase kinase) inhibitor PD 098059 into the hippocampus (HIP), amygdala (AMY), entorhinal cortex (EC) and posterior parietal cortex (PPC). Here we investigate the role 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 the MAPKK inhibitor PD 098059. Adult male Wistar rats were trained and tested in inhibitory avoidance and given an infusion of PD 098059 (0.5, 5.0 or 50.0 microM) at 0, 30, 90, 120, 180, 270 or 360 min after training. A retention 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 training, 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. When infused into the EC, PD 098059 enhanced STM when given at 0 min after training and had no effect when given at 30, 90, 120 or 180 min after training. 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-dependent. These findings indicate that the MAPK cascade in the HIP and EC is differentially involved in short- and long-term retention of inhibitory avoidance in rats.
Rats received, through bilaterally implanted indwelling cannulae, 0.5 microliter infusions of 6-c... more Rats received, through bilaterally implanted indwelling cannulae, 0.5 microliter infusions of 6-cyano-7-nitroquinoxaline2,3-dione (CNQX) (0.5 microgram), D-2-amino-5-phophono pentanoic acid (AP5) (5.0 micrograms), muscimol (0.5 microgram), scopolamine (2.0 micrograms), SCH23390 (2.5 micrograms), saline or a vehicle into the CA1 region of the hippocampus, or into the antero-lateral prefrontal (PRE), posterior parietal (PP) and entorhinal cortex (EC). The infusions were given 6 min prior to one-trial step-down inhibitory avoidance training in order to measure their effect on working memory (WM), or immediately post-training in order to measure their effect on short-term (STM) and long-term memory (LTM), 1.5 and 24 h later, respectively. WM was inhibited by CNQX or muscimol given into any of the cortical areas, by SCH23390 given into CA1, PRE or PP, and by scopolamine given into PRE or EC. STM was unaffected by any of the treatments given into PRE, and was inhibited by CNQX or muscimol given into CA1, PP and EC and by scopolamine given into PP, and enhanced by SCH given into CA1. LTM was inhibited by CNQX, muscimol, scopolamine or SCH23390 given into PRE, by scopolamine given into PP, by SCH23390 given into the entorhinal cortex, and by AP5, CNQX, muscimol or scopolamine given into CA1. The results indicate a differential involvement of the various neurotransmitter systems in the three types of memory in the various brain areas, and a separation of the mechanisms and of the regions involved in each. In addition, some of the findings suggested links between WM and LTM processing in PRE, between WM and STM processing in EC and PP, and between all three types of memory in CA1.
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