The effect of isoproterenol (Iso) on synaptic transmission mediated by the N-methyl-D-aspartate (NMDA) receptors (EPSPNMDA) was investigated in slices of rat amygdala using intracellular recording techniques. EPSPNMDA was isolated pharmacologically by application of a solution containing the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 microM) and GABAA receptor blocker bicuculline (20 microM). Superfusion of Iso (15 microM) produced a long-lasting enhancement of EPSPNMDA. Pretreatment the slices with propranolol (10 microM) completely prevented the effect of Iso confirming the mediation by beta-adrenergic receptors. These results provide the direct evidence for adrenergic modulation of excitatory amino acid neurotransmission in the vertebrate central nervous system.