SB203580, the p38 mitogen-activated protein kinase inhibitor blocks the inhibitory effect of β-amyloid on long-term potentiation in the rat hippocampus

The effect of the beta-amyloid peptide (beta-AP) 25-35 and SB203580, the p38 mitogen-activated protein (MAP) kinase inhibitor, were investigated on long term potentiation (LTP) in the dentate gyrus of the rat hippocampal slice. In the presence of 1 mu M beta-AP (25-35) basal synaptic transmission was reduced to 88.9 +/- 5.2% of control (n = 4, P < 0.5). Tetanic stimulation of control slices gave rise to a robust LTP (139 +/- 4%, n = 5, P < 0.05). 1 mu M beta-AP (25-35) was found to inhibit this LTP (104.0 +/- 4.5% at 90 min; n = 4, P < 0.05). Perfusion of SB203580 alone (1 mu M) had no significant effect on baseline synaptic transmission or LTP (n = 4). However, in the presence of SB203580, beta-AP (25-35; 1 mu M) did not give rise to a reduction in LTP (150 +/- 11.8%, n = 4). These results suggest that high levels of beta-AP (25-35) may inhibit LTP through a pathway involving the p38 MAP kinase. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.