Effect of Riluzole, a Glutamate Release Inhibitor, on Synaptic Plasticity in the Intrahippocampal A[beta] Rat Model of Alzheimer's Disease

Alzheimer's disease (AD) is associated with cognitive deficits of varying degrees and with impairment of the synaptic transmission-related tasks. Pathologically, AD is highlighted with accumulation of extracellular [beta]-amyloid plaques and of neurofibrillary tangles. Glutamate-mediated neurotoxicity plays a pivotal role in the pathogenesis of AD. Deficits of long-term potentiation (LTP) and neuronal synaptic plasticity as an essential mechanism of the learning and memory disorders in AD has been ascribed to over-activation of glutamate receptors. We examined the effect of riluzole, a glutamate release inhibitor, on LTP impairment in the dentate gyrus (DG) in a rat model of AD provided by bilateral intrahippocampal amyloid [beta] (A[beta] 25-35) injections; riluzole was administered at a dose of 10 mg/kg. The LTP in perforant path-DG synapses was evaluated using measurements of the field excitatory postsynaptic potential (fEPSP) slope and population spike (PS) amplitude. We found that A[beta] (25-35) significantly decreased the fEPSP slope and PS amplitude, as compared to those in the sham group; riluzole pretreatment in the A[beta]-microinjected group significantly increased these parameters. Taken together, it is concluded that riluzole could noticeably improve synaptic plasticity and enhance LTP in the rat model of AD.