Elsevier

Neuroscience

Volume 150, Issue 4, 19 December 2007, Pages 818-828
Neuroscience

Behavioural neuroscience
Activation of basolateral amygdala corticotropin-releasing factor 1 receptors modulates the consolidation of contextual fear

https://doi.org/10.1016/j.neuroscience.2007.10.001Get rights and content

Abstract

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 (CRF1) receptors in comparison to the CeA. However, the role of BLA CRF1 receptors in contextual fear conditioning is poorly understood. In the present study, we first demonstrated in rats that oral administration of DMP696, the selective CRF1 receptor antagonist, had no significant effects on the acquisition of contextual fear but produced a subsequent impairment in contextual freezing suggesting a role of CRF1 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 CRF1 receptors in activating the fear memory consolidation process, which may involve BLA pCREB-induced synaptic plasticity.

Section snippets

Experimental animals

Subjects were adult male Long-Evans rats (245–310 g) bred at the University of Hawaii Animal Facility from stock obtained from Charles River Laboratories (Raleigh, NC, USA). Rats were individually housed in polycarbonate cages 1 week prior to the experiments and maintained on a 12-h light/dark schedule with lights on at 06:00 h. Each cage was provisioned with food, water and a layer of Sani-chips. Animal testing occurred between 08:00 and 12:00 h. All procedures were approved by the University

Acquisition test

Rats treated with different doses of DMP696 showed very little freezing during the 2-min preshock interval. However, administration of foot shock increased the duration of contextual freezing across the first three post-shock acquisition intervals, F(5,175)=214.42, P<0.001 (Fig. 1A), and freezing remained at high levels from post-shock intervals 3–5. The overall duration of freezing did not differ significantly in rats treated with different doses of DMP696, F(4,35)=1.56, P>0.05. In addition,

Discussion

The present results demonstrate that CRF1 receptors, and more specifically BLA CRF1 receptors, play an important role in the consolidation of emotional memory. We first showed that oral administration of DMP696, the selective CRF1 receptor antagonist, prior to the acquisition of contextual fear conditioning subsequently produced a dose-dependent reduction in the drug-free conditioned freezing test without significant behavioral effects on the acquisition of contextual freezing. Another study

Conclusion

The present experiments provide new information implicating BLA CRF1 receptors in the consolidation of contextual fear memory. These results expand the list of other neurotransmitter (e.g. norepinephrine, acetylcholine) and hormone (e.g. corticosterone) receptor systems that may have unique or additional cellular actions in BLA cells participating in the consolidation of emotional experiences (McGaugh 2004, Pare 2003, Roozendaal 2000). Importantly, the ability to compromise the consolidation of

Acknowledgments

The research was supported by National Institutes of Health grant NS39406.

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