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 ac tions of forskolin and cyclic adenosine-3',5'-monophosphate (cAMP) ana logues on the N-methyl-D-aspartate (NMDA) receptor-mediated synaptic p otential (EPSP(NMDA)), Intracellular recordings were made from basolat eral 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 an d persistently potentiated the EPSP(NMDA). In contrast, the inactive f orskolin analogue, 1,9-dideoxy-forskolin, failed to affect the EPSP(NM DA) significantly. Superfusion of dibutyryl-cAMP (dbcAMP, 200 mu M) fo r 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 sele ctive A(1) receptor antagonist, blocked the transient depressive phase produced by dbcAMP, This result suggests that the transient depressio n induced by dbcAMP was likely due to the interaction of dbcAMP or its breakdown products with adenosine A(1) receptors. To determine the si te of action, we examined the effect of forskolin on the postsynaptic responses to exogenously applied NMDA. Forskolin potentiated the posts ynaptic depolarization induced by NMDA, suggesting that the enhancemen t is mediated, at least in part, by a persistent upregulation of posts ynaptic NMDA receptor-operated conductances. Occlusion experiments wer e performed to examine whether the sustained enhancements of EPSP(NMDA ) produced by tetanic stimulation (TS) and forskolin share a common me chanism. 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 enh anced 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.