Activation of Basolateral Amygdala Corticotropin-releasing Factor 1 Receptors Modulates the Consolidation of Contextual Fear

The basolateral amygdala complex (BLA) and central amygdala nucleus (CeA) are involved in fear and anxiety. In addition, the BLA contains a high density of corticotropin-releasing factor 1 (CRF(1)) receptors in comparison to the CeA. However, the role of BLA CRF(1) receptors in contextual fear conditioning is poorly understood. In the present study, we first demonstrated in rats that oral administration of DMP696, the selective CRF(1) receptor antagonist, had no significant effects on the acquisition of contextual fear but produced a subsequent impairment in contextual freezing suggesting a role of CRF(1) receptors in the fear memory consolidation process. In addition, oral administration of DMP696 significantly reduced phosphorylation of cyclic AMP response element-binding protein (pCREB) in the lateral and basolateral amygdala nuclei, but not in the CeA, during the post-fear conditioning period. We then demonstrated that bilateral microinjections of DMP696 into the BLA produced no significant effects on the acquisition of conditioned fear but reduced contextual freezing in a subsequent drug-free conditioned fear test. Importantly, bilateral microinjections of DMP696 into the BLA at 5 min or 3 h, but not 9 h, after exposure to contextual fear conditioning was also effective in reducing contextual freezing in the conditioned fear test. Finally, microinfusions of either DMP696 into the CeA or a specific corticotropin-releasing factor 2 receptor antagonist in the BLA were shown to have no major effects on disrupting either contextual fear conditioning or performance of contextual freezing in the drug-free conditioned fear test. Collectively, results implicate a role of BLA CRF(1) receptors in activating the fear memory consolidation process, which may involve BLA pCREB-induced synaptic plasticity.