Noradrenergic-glucocorticoid modulation of emotional memory encoding in the human hippocampus

• Published in: Psychological medicine 2011-10, Vol.41 (10), p.2167-2176
• Main Authors: Kukolja, J., Klingmüller, D., Maier, W., Fink, G. R., Hurlemann, R.
• Format: Article
• Language: English
• Subjects: Adrenergic Uptake Inhibitors - pharmacology; Amygdala - drug effects; Analysis of Variance; Anti-Inflammatory Agents - pharmacology; Autobiographical memory; Biological and medical sciences; Brain; Double-Blind Method; Drug Therapy, Combination; Emotions; Encoding; Glucocorticoids; Hippocampus; Hippocampus - drug effects; Humans; Hydrocortisone - pharmacology; Magnetic Resonance Imaging; Medical sciences; Memory; Memory - drug effects; Memory - physiology; Morpholines - pharmacology; Neurobiology; Placebos; Psychiatry; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Recognition (Psychology) - drug effects; Steroids; Stress; Traumatic stress
• ISSN: 0033-2917; 1469-8978
• DOI: 10.1017/S0033291711000183

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. 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. 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. 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.