PAIRED-PULSE DEPRESSION OF THE N-METHYL-D-ASPARTATE RECEPTOR-MEDIATED SYNAPTIC POTENTIALS IN THE AMYGDALA

1 An in vitro slice preparation of rat amygdala was used to study the paired-pulse depression of the N-methyl-D-aspartate (NMDA) receptor-mediated synaptic potential e.p.s.p.(NMDA). 2 The e.p.s.p.(NMDA) was isolated pharmacologically by applying a solution containing the non-NMDA receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and the gamma-aminobutyric acid(A) (GABA(A)) blocker picrotoxin and increasing the stimulus intensity. 3 When two stimuli of identical strength were applied in close succession, the second e.p.s.p.(NMDA) was depressed. This paired-guise depression was seen with interstimulus intervals of between 100 ms and 2000 ms; the maximal depression was observed at interval of 200 ms. 4 Superfusion of phaclofen or 2-hydroxy-saclofen inhibited the paired-pulse depression indicating the involvement of GABA(B) receptors. 5 Bath applications of Ba2+ or intracellular injection of Cs+ to block post- but not presynaptic GABA(B) receptors failed to inhibit the paired-pulse depression (PPD). 6 Incubation of slices with pertussis toxin prevented the postsynaptic hyperpolarization induced by baclofen. The PPD of e.p.s.p.(NMDA), however, was not affected by pertussis toxin treatment. 7 These results suggest that GABA released by the first stimulus acts on GABA(B) receptors to suppress the second e.p.s.p.(NMDA) via mechanisms other than activation of a postsynaptic GABA(B) receptor-coupled K+ conductance.