a1 Department of Psychiatry, University of Bonn, Bonn, Germany
a2 Cognitive Neurology Section, Institute of Neuroscience and Medicine (INM-3), Research Center Jülich, Jülich, Germany
a3 Department of Neurology, University Hospital, Cologne University, Cologne, Germany
a4 Department of Clinical Biochemistry, Division of Endocrinology, University of Bonn, Bonn, Germany
Background Current rodent models emphasize the joint action of the stress mediators noradrenaline (NE) and cortisol (CORT) in conferring a memory advantage of emotional over neutral stimuli.
Method Using a pharmacological strategy of tackling this stress-related mechanism to enhance human episodic (autobiographical) memory, we measured amygdala-hippocampal responses during encoding of emotional and neutral stimuli with functional magnetic resonance imaging in 51 healthy subjects under four pharmacological conditions in a double-blind parallel group design: (i) placebo; (ii) the NE-reuptake inhibitor reboxetine (4 mg); (iii) hydrocortisone (synthetic CORT) (30 mg); or (iv) both agents in combination.
Results Differential drug effects were found in the left hippocampus, whereas hydrocortisone alone selectively decreased hippocampal responses to emotional relative to neutral stimuli, reboxetine potentiated hippocampal responses to these stimuli. Importantly, the inhibitory influence of hydrocortisone was reversed by co-administration of reboxetine.
Conclusions Our results imply that stress levels of CORT alone attenuate hippocampal responses to emotional stimuli, an effect possibly related to a regulatory negative feedback loop. However, when simultaneously elevated to stress levels, NE and CORT act together to synergistically enhance hippocampal activity during encoding of emotional stimuli, a mechanism that may turn maladaptive under circumstances of traumatic stress.
(Received July 27 2010)
(Revised January 12 2011)
(Accepted January 18 2011)
(Online publication March 04 2011)