Abstract
Conventional intracellular recordings were used to monitor postsynaptic potentials of basolateral amygdala neurones (BLA) in brain slices comprising the BLA, the entorhinal cortex (EC) and the hippocampus, in which the EC-BLA connections were preserved. Stimulation of the BLA with a bipolar electrode elicited complex postsynaptic potentials consisting of α-amino-3-hydroxy-5-methyl-isoxazoleproprionic acid (AMPA) receptor-mediated fast excitatory postsynaptic potentials (fast EPSPs), γ-amino-butyric acid (GABA
A) receptor-mediated fast inhibitory postsynaptic potentials (fast IPSPs) and GABA
B receptormediated slow IPSPs. Bath application of 10 μM of the AMPA receptor antagonist 6-cyano-7-nitroquinoxaline-2, 3-dione and of 10 μM of the GABA
A receptor antagonist bicuculline methiodide (BMI) revealed a
N-methyl-D-aspartate (NMDA) receptor-mediated slow EPSPs, which was occasionally followed by a GABA
B receptormediated slow IPSPs. Under these conditions, the log concentration-response curve for
d-(E)-2-amino-4-methyl-5-phosphono-3-pentanoic acid (CGP 40 116), a newly developed drug with proposed NMDA-receptor antagonist properties, was compared to that obtained with the ‘classic’ antagonist D(−)-2-amino-5-phosphonopentanoic acid (
d-AP5) in inhibiting the NMDA-mediated postsynaptic potentials. CGP 40 116 (
ic
50: 130 nM) was over 30 times more potent than
d-AP5 (
ic
50: 4100 nM) in reducing NMDA-mediated slow EPSP. In conclusion, the present study indicates that CGP 40 116, a new orally-active NMDA antagonist, shows a very high potency on NMDA receptors in the amygdala and may therefore be a valuable tool for studying the behavioural effect of NMDA-receptor mediated transmission in this structure.