LAMOTRIGINE INHIBITS TETRAETHYLAMMONIUM-INDUCED SYNAPTIC PLASTICITY IN THE RAT AMYGDALA

Although long-term potentiation was generally initiated by a brief tet anus, in the hippocampus, it could also be evoked by application of th e K+ channel blocker tetraethylammonium. The present study was aimed a t investigating the effect of lamotrigine, a new anticonvulsant, on th e tetraethylammonium-induced potentiation in brain slices of the rat a mygdala using intracellular recording techniques. Bath application of tetraethylammonium (20 mM) for 10 min resulted in a long-lasting enhan cement of the amplitude of excitatory postsynaptic potentials to 235+/ -12% of control (n=6, P<0.001). Pretreatment of the slices with nifedi pine (10 mu M) abolished the potentiation, suggesting that tetraethyla mmonium long-term potentiation in the amygdala is due to Ca2+ influx t hrough voltage-dependent Ca2+ channels. By contrast, N-methyl-D-aspart ate receptor activation was not required because D-2-amino-5-phosphono valerate (50 mu M) did not prevent the tetraethylammonium long-term po tentiation. Superfusion of lamotrigine (50 mu M) depressed the excitat ory postsynaptic potential to 53.8+/-3.9% of control. Tetraethylammoni um was subsequently added in the presence of lamotrigine but Failed to enhance the excitatory postsynaptic potential. Bursts of Ca2+ spikes evoked by a depolarizing pulse or by synaptic stimulation under tetrae thylammonium were depressed by lamotrigine. It is concluded that lamot rigine is capable of inhibiting tetraethylammonium-induced synaptic pl asticity. The underlying mechanism is likely due to lamotrigine's inhi bition of postsynaptic voltage-dependent Ca2+ channels. Considering th at tetraethylammonium is a convulsant agent and brief seizure episodes induced long-term potentiation, fibre sprouting and the development o f aberrant synaptic contacts, lamotrigine could be a potential neuropr otective agent, especially in pathological situations where excessive glutamate release occurs. (C) 1997 IBRO. Published by Elsevier Science Ltd.