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 (EPSPNMDA). Intracellular recordings were made from basolateral amygdala neurons in the presence of 6-cyano-7-nitroquinoxaline-2,3-di-one (CNQX, 10 microM) and picrotoxin (50 microM) to pharmacologically isolate the EPSPNMDA. Application of forskolin (25 microM) markedly and persistently potentiated the EPSPNMDA. In contrast, the inactive forskolin analogue, 1,9-dideoxy-forskolin, failed to affect the EPSPNMDA significantly. Superfusion of dibutyryl-cAMP (dbcAMP, 200 microM) for 15 min caused a transient depression of the amplitude of EPSPNMDA. The EPSPNMDA 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-dipropyl-xanthine (DPCPX, 5 microM), a selective A1 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 A1 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.(ABSTRACT TRUNCATED AT 250 WORDS)