CYCLIC ADENOSINE-3',5'-MONOPHOSPHATE POTENTIATES THE SYNAPTIC POTENTIAL MEDIATED BY NMDA RECEPTORS IN THE AMYGDALA

An in vitro slice preparation of rat amygdala was used to study the actions of forskolin and cyclic adenosine-3',5'-monophosphate (cAMP) analogues on the N-methyl-D-aspartate (NMDA) receptor-mediated synaptic potential (EPSP(NMDA)), Intracellular recordings were made from basolateral amygdala neurons in the presence of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 mu M) and picrotoxin (50 mu M) to pharmacologically isolate the EPSP(NMDA). Application of forskolin (25 mu M) markedly and persistently potentiated the EPSP(NMDA). In contrast, the inactive forskolin analogue, 1,9-dideoxy-forskolin, failed to affect the EPSP(NMDA) significantly. Superfusion of dibutyryl-cAMP (dbcAMP, 200 mu M) for 15 min caused a transient depression of the amplitude of EPSP(NMDA). The EPSP(NMDA) amplitude was reduced to 68 +/- 3% of control (n = 10) 15 min after the application, restored to its control value within 25 min, and followed by a long-term potentiation (LTP). Pretreating the slices with 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 5 mu M), a selective A(1) receptor antagonist, blocked the transient depressive phase produced by dbcAMP, This result suggests that the transient depression induced by dbcAMP was likely due to the interaction of dbcAMP or its breakdown products with adenosine A(1) receptors. To determine the site of action, we examined the effect of forskolin on the postsynaptic responses to exogenously applied NMDA. Forskolin potentiated the postsynaptic depolarization induced by NMDA, suggesting that the enhancement is mediated, at least in part, by a persistent upregulation of postsynaptic NMDA receptor-operated conductances. Occlusion experiments were performed to examine whether the sustained enhancements of EPSP(NMDA) produced by tetanic stimulation (TS) and forskolin share a common mechanism. Three episodes of TS were delivered to saturate the LTP and, under this condition, forskolin still caused a further potentiation of the EPSP(NMDA). Similarly, TS, delivered after the EPSP(NMDA) was enhanced by forskolin or dbcAMP, produced LTP. These results suggest that the longterm enhancements of EPSP(NMDA), produced by TS and forskolin are different and thus do not support the hypothesis that activation of protein kinase A triggers LTP. (C) 1995 Wiley-Liss, Inc.