Effects of lamotrigine on field potentials and long-term potentiation in guinea pig hippocampal slices

PURPOSE: To investigate the effects of lamotrigine (LTG), a new anticonvulsant, on neuronal excitability, synaptic transmission, and long-term potentiation (LTP) in guinea pig hippocampal slices. METHODS: Electrically evoked field excitatory postsynaptic potentials (fEPSPs) and population spikes (PSs) were investigated in the CA1 region of the hippocampus. RESULTS: The concentration-response curves showed different actions of LTG in concentrations near therapeutic plasma levels (10 microM) on fEPSPs and PSs. The initial slopes of fEPSPs were not affected, whereas the amplitudes of PSs were significantly decreased. Higher concentrations of LTG decreased both fEPSP slopes and PS amplitudes; however, the effects on PSs were much stronger. Also, there were no differences in fEPSP slopes or PS amplitudes compared with controls when LTP was induced in the presence of LTG (10 microM). CONCLUSIONS: Our data are in contrast to previous findings that suggest LTG acts primarily on presynaptic sites by blocking the release of excitatory amino acids. Further, LTP was not affected by LTG.