Presynaptic inhibition of excitatory neurotransmission by lamotrigine in the rat amygdalar neurons

Su Jane Wang, Chiung Chun Huang, Kuei-Sen Hsu, Jing Jane Tsai, Po-Wu Gean

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62 Citations (Scopus)

Abstract

Lamotrigine (LAG) is a new antiepileptic drug which is licensed as adjunctive therapy for partial and secondary generalized seizures. In the present study, the mechanisms responsible for its antiepileptic effect were studied in rat amygdaloid slices using intracellular recording and whole- cell patch clamp techniques. Bath application of LAG (50 μM) reversibly suppressed the excitatory postsynaptic potentials (EPSPs) and currents (EPSCs) evoked by stimulating ventral endopyriform nucleus. Synaptic response mediated by the N-methyl-D-aspartate (NMDA) receptor (EPSP(NMDA)) was isolated pharmacologically by application of a solution containing non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 μM) and γ-aminobutyric acid(A) receptor antagonist bicuculline (20 μM). LAG produced a parallel inhibition of EPSP(NMDA). Postsynaptic depolarization induced by α-amino-5-methyl-4-isoxazole propionate (AMPA) was not altered by LAG. In addition, LAG increased the ratio of the second pulse response to the first pulse response (P2/P1), which is consistent with a presynaptic mode of action. The L-type Ca2+ channel blocker nifedipine (20 μM) had no effect on LAG-induced presynaptic inhibition. However, the depressant effect of LAG was markedly reduced in slices pretreated with N-type Ca2+ channel blocker ω-conotoxin-GVIA (ω-CgTX-GVIA, 1 μM) or a broad spectrum Ca++ channel blocker ω-conotoxin-MVIIC (ω-CgTX-MVIIC, 1 μM). It is concluded that a reduction in ω-CgTX-GVIA-sensitive Ca2+ currents largely contributes to LAG-induced presynaptic inhibition.

Original languageEnglish
Pages (from-to)248-255
Number of pages8
JournalSynapse
Volume24
Issue number3
DOIs
Publication statusPublished - 1996 Nov 1

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Physiology
  • Pharmacology

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