期刊
JOURNAL OF NEUROSCIENCE
卷 28, 期 26, 页码 6642-6651出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.1336-08.2008
关键词
alpha-helical CRF9-41; atenolol; CRF; CRF6-33; CRF-binding protein; corticosterone; emotional arousal; norepinephrine; inhibitory avoidance
资金
- NIMH NIH HHS [MH12526, R56 MH012526, R01 MH012526, R01 MH012526-40A1] Funding Source: Medline
Extensive evidence indicates that stress hormone effects on the consolidation of emotionally influenced memory involve noradrenergic activation of the basolateral complex of the amygdala (BLA). The present experiments examined whether corticotropin-releasing factor (CRF) modulates memory consolidation via an interaction with the beta-adrenoceptor-cAMP system in the BLA. In a first experiment, male Sprague Dawley rats received bilateral infusions of the CRF-binding protein ligand inhibitor CRF6-33 into the BLA either alone or together with the CRF receptor antagonist alpha-helical CRF9-41 immediately after inhibitory avoidance training. CRF6-33 induced dose-dependent enhancement of 48 h retention latencies, which was blocked by coadministration of alpha-helical CRF9-41, suggesting that CRF6-33 enhances memory consolidation by displacing CRF from its binding protein, thereby increasing free endogenous CRF concentrations. In a second experiment, intra-BLA infusions of atenolol (beta-adrenoceptor antagonist) and Rp-cAMPS (cAMP inhibitor), but not prazosin (alpha(1)-adrenoceptor antagonist), blocked CRF6-33-induced retention enhancement. In a third experiment, the CRF receptor antagonist alpha-helical CRF9-41 administered into the BLA immediately after training attenuated the dose-response effects of concurrent intra-BLA infusions of clenbuterol (beta-adrenoceptor agonist). In contrast, alpha-helical CRF9-41 did not alter retention enhancement induced by posttraining intra-BLA infusions of either cirazoline (alpha(1)-adrenoceptor agonist) or 8-br-cAMP (cAMP analog). These findings suggest that CRF facilitates the memory-modulatory effects of noradrenergic stimulation in the BLA via an interaction with the beta-adrenoceptor-cAMP cascade, at a locus between the membrane-bound beta-adrenoceptor and the intracellular cAMP formation site. Moreover, consistent with evidence that glucocorticoids enhance memory consolidation via a similar interaction with the beta-adrenoceptor-cAMP cascade, a last experiment found that the CRF and glucocorticoid systems within the BLA interact in influencing beta-adrenoceptor-cAMP effects on memory consolidation.
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