beta-Amyloid produces a delayed NMDA receptor-dependent reduction in synaptic transmission in rat hippocampus.

The delayed effect of in vivo injection of beta-amyloid on glutamatergic synaptic transmission was investigated in the rat hippocampus. The amplitude of field excitatory postsynaptic potentials recorded in the CA1 region of awake rats was reduced 24 h after the injection of beta-amyloid (1-40) (0.4 or 3.5 nmol i.c.v.). The effect lasted for at least 5 days and was prevented by treatment with the N-methyl-D-aspartate (NMDA) receptor antagonist CPP (7 mg kg-1 x 2, i.p.). Similar results were obtained ex vivo in the dentate gyrus. There was no change in the ability to induce long-term potentiation. These results provide direct evidence that beta-amyloid produced a delayed reduction in the function of glutamatergic synapses, probably as a result of an initial over-activation of the NMDA receptor-mediated component of transmission.