PAIRED-PULSE DEPRESSION OF THE N-METHYL-D-ASPARTATE RECEPTOR-MEDIATEDSYNAPTIC 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-me diated synaptic potential e.p.s.p.(NMDA). 2 The e.p.s.p.(NMDA) was iso lated 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 increa sing the stimulus intensity. 3 When two stimuli of identical strength were applied in close succession, the second e.p.s.p.(NMDA) was depres sed. This paired-guise depression was seen with interstimulus interval s of between 100 ms and 2000 ms; the maximal depression was observed a t interval of 200 ms. 4 Superfusion of phaclofen or 2-hydroxy-saclofen inhibited the paired-pulse depression indicating the involvement of G ABA(B) receptors. 5 Bath applications of Ba2+ or intracellular injecti on of Cs+ to block post- but not presynaptic GABA(B) receptors failed to inhibit the paired-pulse depression (PPD). 6 Incubation of slices w ith pertussis toxin prevented the postsynaptic hyperpolarization induc ed by baclofen. The PPD of e.p.s.p.(NMDA), however, was not affected b y pertussis toxin treatment. 7 These results suggest that GABA release d by the first stimulus acts on GABA(B) receptors to suppress the seco nd e.p.s.p.(NMDA) via mechanisms other than activation of a postsynapt ic GABA(B) receptor-coupled K+ conductance.