A role for amygdaloid PKA and PKC in the acquisition of long-term conditional fear memories in rats

Although there is great interest in the cellular mechanisms underlying Pavl ovian conditioning, few studies have directly examined the contribution of intracellular signaling pathways in the amygdala to the acquisition and exp ression of conditional fear memories. In the present study, we examined thi s issue by infusing 1-(5'-isoquinolinesulfonyl)-2-methylpiperazine (H7), a potent inhibitor of both protein kinase C (PE(C) and cAMP-dependent protein kinase (PKA), directly into the amygdala prior to fear conditioning or ret ention testing. We found that infusion of H7 prior to training attenuated l ong-term conditional fear in a dose-dependent manner (Experiment 1), but sh ort-term fear memories were spared. The contribution of protein kinases to conditional fear was region-specific within the amygdala: infusion of H7 in to the basolateral amygdala (BLA) but not the central nucleus of the amygda la (CEA) resulted in attenuated freezing (Experiment 2). Moreover, the defi cits in fear conditioning produced by PKA/PKC inhibition were not modality- specific, insofar as intra-BLA H7 reduced both contextual and auditory fear . The effects of H7 on conditional freezing were not attributable to either state-dependency or performance deficits (Experiment 3). Together, these e xperiments suggest that amygdaloid PKA and PKC play an important role in th e acquisition of fear memories. (C) 2000 Elsevier Science B.V. All rights r eserved.