INDUCTION OF HIPPOCAMPAL LONG-TERM POTENTIATION BY ALPHA-TOCOPHEROL

Long-term potentiation (LTP) of synaptic transmission in the hippocampus is thought to be one of the cellular mechanisms underlying learning and memory. Recent evidence in literature suggests the involvement of free radicals in impeding LTP maintenance. In the present study, the effects of alpha-tocopherol, a major lipid-soluble antioxidant which could prevent lipid peroxidation, were examined on the excitatory post-synaptic potentials (EPSPs) of CA1 neurons in guinea pig hippocampal slices. Alpha-Tocopherol phosphate disodium salt (0.2 mM applied for 5 min) induced a slowly developing long-lasting increase of the EPSP, without significantly changing the membrane potential, the input resistance and the ability to generate action potentials. No significant changes in the fast and the slow inhibitory post-synaptic potentials (IPSPs) were observed during the alpha-tocopherol-induced LTP of the EPSP. 2-Amino-5-phosponovalerate (APV) did not block the induction of this LTP. L-Ascorbic acid (Na salt, 3-10 mM), a water-soluble antioxidant, failed to produce any significant enhancement in the EPSP. These results indicate that alpha-tocopherol can induce LTP of the EPSP in guinea pig hippocampal CA1 neurons. The activation of N-methyl-D-aspartate (NMDA) receptors does not appear to be necessary for this action of a-tocopherol. Whether the LTP-inducing action of this agent is related to its antioxidant property is unclear.