ENHANCEMENT OF NMDA RECEPTOR-MEDIATED SYNAPTIC POTENTIAL BY ISOPROTERENOL IS BLOCKED BY RP-ADENOSINE 3',5'-CYCLIC MONOPHOSPHOTHIOATE

The intracellular mechanisms underlying the facilitatory action of isoproterenol (Iso) on the NMDA receptor-mediated synaptic potential (EPSP(NMDA)) was investigated in an in vitro slice preparation of rat amygdala. Intracellular recordings were made from basolateral amygdala neurons in the presence of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 muM) and picrotoxin (50 muM) which block non-NMDA and GABA(A) receptors, respectively. Superfusion of Iso (15 muM) produced a sustained increase in EPSP(NMDA). Rp-adenosine-3',5'-cyclic monophosphothioate (Rp-cAMPS), a potent inhibitor of protein kinase A (PKA) alone decreased the amplitude of EPSP(NMDA) below baseline values and prevented the subsequent potentiation by Iso. Forskolin, a direct activator of adenylate cyclase, mimics the effect of Iso, and Rp-cAMPS also reversed forskolin-induced enhancement of EPSP(NMDA). These results suggest that cAMP-dependent protein kinase mediates the enhancement of EPSP(NMDA) by Iso in the amygdala.