Noradrenergic mediation of the memory-enhancing effect of corticotropin-releasing factor in the locus coeruleus of rats

Abstract

A role for the locus coeruleus (LC) in attention and behavioral arousal has been suggested. The present study examined the effect of corticotropin-releasing factor (CRF) in the LC on memory retention of a passive-avoidance task in rats. Our results indicate that intra-LC CRF injection significantly improved retention performance. Decreases of norepinephrine (NE) levels in the hippocampus and the amygdala occurred in these animals. Intra-hippocampal 6-hydroxydopamine pretreatment did not affect memory alone, while it antagonized the memory-enhancing effect of CRF in the LC. This finding suggests that the dorsal NE pathway is involved in the memory consolidation process. Similar to the effect of CRF, application of the α 2-adrenergic antagonist yohimbine to the LC also dose-dependently enhanced memory, suggesting that CRF improved memory through activation of NE neurons in the LC. Finally, the anxiolytic chlordiazepoxide, at a concentration that did not alter memory by itself, prevented the memory-facilitating effect of CRF in the LC. Our findings suggest that the LC is an important structure in modulating learning and memory processes of passive avoidance learning in rats. CRF may enhance memory through activation of NE neurons in the LC and, at least in part, through the dorsal NE pathway. Furthermore, the LC is probably an anatomical substrate for anxiety and intra-LC CRF may enhance memory through its anxiogenic actions.