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 acidA (GABAA) 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-pulse 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 GABAB receptors. 5. Bath applications of Ba2+ or intracellular injection of Cs+ to block post- but not presynaptic GABAB 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 GABAB receptors to suppress the second e.p.s.p.NMDA via mechanisms other than activation of a postsynaptic GABAB receptor-coupled K+ conductance.
