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

Published online by Cambridge University Press:  04 March 2011

J. Kukolja ,
D. Klingmüller ,
W. Maier ,
G. R. Fink  and
R. Hurlemann
J. Kukolja*
Affiliation:
Department of Psychiatry, University of Bonn, Bonn, Germany Cognitive Neurology Section, Institute of Neuroscience and Medicine (INM-3), Research Center Jülich, Jülich, Germany Department of Neurology, University Hospital, Cologne University, Cologne, Germany
D. Klingmüller
Affiliation:
Department of Clinical Biochemistry, Division of Endocrinology, University of Bonn, Bonn, Germany
W. Maier
Affiliation:
Department of Psychiatry, University of Bonn, Bonn, Germany
G. R. Fink
Affiliation:
Cognitive Neurology Section, Institute of Neuroscience and Medicine (INM-3), Research Center Jülich, Jülich, Germany Department of Neurology, University Hospital, Cologne University, Cologne, Germany
R. Hurlemann
Affiliation:
Department of Psychiatry, University of Bonn, Bonn, Germany
*
*Address for correspondence: J. Kukolja, M.D., Department of Neurology, University of Cologne, Kerpener Str. 62, 50924 Cologne, Germany. (Email: [email protected])
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Abstract

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.

Keywords

CortisolemotionfMRIhippocampusmemorynoradrenalinestress
Type
Original Articles
Information
Psychological Medicine , Volume 41 , Issue 10 , October 2011 , pp. 2167 - 2176
Copyright
Copyright © Cambridge University Press 2011

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References

Abercrombie, HC, Kalin, NH, Thurow, ME, Rosenkranz, MA, Davidson, RJ (2003). Cortisol variation in humans affects memory for emotionally laden and neutral information. Behavioral Neuroscience 117, 505–516.CrossRefGoogle ScholarPubMed
Amunts, K, Kedo, O, Kindler, M, Pieperhoff, P, Mohlberg, H, Shah, NJ, Habel, U, Schneider, F, Zilles, K (2005). Cytoarchitectonic mapping of the human amygdala, hippocampal region and entorhinal cortex: intersubject variability and probability maps. Anatomy and Embryology (Berl) 210, 343–352.CrossRefGoogle ScholarPubMed
Brewin, CR (2008). What is it that a neurobiological model of PTSD must explain? Progress in Brain Research 167, 217–228.CrossRefGoogle ScholarPubMed
Buchanan, TW, Lovallo, WR (2001). Enhanced memory for emotional material following stress-level cortisol treatment in humans. Psychoneuroendocrinology 26, 307–317.CrossRefGoogle ScholarPubMed
Burgess, N, Maguire, EA, O'Keefe, J (2002). The human hippocampus and spatial and episodic memory. Neuron 35, 625–641.CrossRefGoogle ScholarPubMed
Cahill, L, Prins, B, Weber, M, McGaugh, JL (1994). Beta-adrenergic activation and memory for emotional events. Nature 371, 702–704.CrossRefGoogle ScholarPubMed
Chamberlain, SR, Muller, U, Blackwell, AD, Clark, L, Robbins, TW, Sahakian, BJ (2006). Neurochemical modulation of response inhibition and probabilistic learning in humans. Science 311, 861–863.CrossRefGoogle ScholarPubMed
Diamond, DM, Campbell, AM, Park, CR, Halonen, J, Zoladz, PR (2007). The temporal dynamics model of emotional memory processing: a synthesis on the neurobiological basis of stress-induced amnesia, flashbulb and traumatic memories, and the Yerkes-Dodson law. Neural Plasticity 60803, 1–33.CrossRefGoogle Scholar
Dolcos, F, LaBar, KS, Cabeza, R (2004). Interaction between the amygdala and the medial temporal lobe memory system predicts better memory for emotional events. Neuron 42, 855–863.CrossRefGoogle ScholarPubMed
Eickhoff, SB, Stephan, KE, Mohlberg, H, Grefkes, C, Fink, GR, Amunts, K, Zilles, K (2005). A new SPM toolbox for combining probabilistic cytoarchitectonic maps and functional imaging data. Neuroimage 25, 1325–1335.CrossRefGoogle ScholarPubMed
Goossens, L, Kukolja, J, Onur, OA, Fink, GR, Maier, W, Griez, E, Schruers, K, Hurlemann, R (2009). Selective processing of social stimuli in the superficial amygdala. Human Brain Mapping 30, 3332–3338.CrossRefGoogle ScholarPubMed
Green, DM, Swets, JA (1966). Signal Detection Theory and Biophysics. Wiley: New York.Google Scholar
Het, S, Ramlow, G, Wolf, OT (2005). A meta-analytic review of the effects of acute cortisol administration on human memory. Psychoneuroendocrinology 30, 771–784.CrossRefGoogle ScholarPubMed
Hurlemann, R (2008). Noradrenergic-glucocorticoid mechanisms in emotion-induced amnesia: from adaptation to disease. Psychopharmacology (Berlin) 197, 13–23.CrossRefGoogle ScholarPubMed
Hurlemann, R, Hawellek, B, Matusch, A, Kolsch, H, Wollersen, H, Madea, B, Vogeley, K, Maier, W, Dolan, RJ (2005). Noradrenergic modulation of emotion-induced forgetting and remembering. Journal of Neuroscience 25, 6343–6349.CrossRefGoogle ScholarPubMed
Hurlemann, R, Matusch, A, Hawellek, B, Klingmuller, D, Kolsch, H, Maier, W, Dolan, RJ (2007). Emotion-induced retrograde amnesia varies as a function of noradrenergic-glucocorticoid activity. Psychopharmacology (Berlin) 194, 261–269.CrossRefGoogle ScholarPubMed
Hurlemann, R, Walter, H, Rehme, AK, Kukolja, J, Santoro, SC, Schmidt, C, Schnell, K, Musshoff, F, Keysers, C, Maier, W, Kendrick, KM, Onur, OA (2010). Human amygdala reactivity is diminished by the beta-noradrenergic antagonist propranolol. Psychological Medicine 40, 1839–1848.CrossRefGoogle ScholarPubMed
Joels, M, Pu, Z, Wiegert, O, Oitzl, MS, Krugers, HJ (2006). Learning under stress: how does it work? Trends in Cognitive Sciences 10, 152–158.CrossRefGoogle ScholarPubMed
Kent, JM (2000). SNaRIs, NaSSAs, and NaRIs: new agents for the treatment of depression. Lancet 355, 911–918.CrossRefGoogle ScholarPubMed
Kiebel, S, Holmes, AP (2003). The General Linear Model. In Human Brain Function (ed. Frackowiak, R. S. J., Friston, K., Frith, C. D., Dolan, R. J., Price, C. J., Ashburner, J. and Penny, W. D.), pp. 725–760. Academic Press: San Diego.Google Scholar
Kukolja, J, Schläpfer, TE, Keysers, C, Klingmüller, D, Maier, W, Fink, GR, Hurlemann, R (2008 a). Modeling a negative response bias in the human amygdala by noradrenergic-glucocorticoid interactions. Journal of Neuroscience 28, 12868–12876.CrossRefGoogle ScholarPubMed
Kukolja, J, Thiel, CM, Wolf, OT, Fink, GR (2008 b). Increased cortisol levels in cognitively challenging situations are beneficial in young but not older subjects. Psychopharmacology (Berlin) 201, 293–304.CrossRefGoogle Scholar
LaBar, KS, Cabeza, R (2006). Cognitive neuroscience of emotional memory. Nature Reviews Neuroscience 7, 54–64.CrossRefGoogle ScholarPubMed
Lang, PJ, Bradley, MM, Cuthbert, BN (2008). International affective picture system (IAPS): affective ratings of pictures and instruction manual. Technical Report A-8. University of Florida: Gainesville, FL.Google Scholar
McGaugh, JL, Roozendaal, B (2002). Role of adrenal stress hormones in forming lasting memories in the brain. Current Opinion in Neurobiology 12, 205–210.CrossRefGoogle ScholarPubMed
Macmillan, NA (1993). Signal detection theory as data analysis method and psychological decision model. In A Handbook for Data Analysis in the Behavioral Sciences: Methodological Issues (ed. Keren, G. and Lewis, C.), pp. 21–57. Erlbaum: Hillsdale, NJ.Google Scholar
Onur, OA, Walter, H, Schlaepfer, TE, Rehme, AK, Schmidt, C, Keysers, C, Maier, W, Hurlemann, R (2009). Noradrenergic enhancement of amygdala responses to fear. Social Cognitive and Affective Neuroscience 4, 119–126.CrossRefGoogle ScholarPubMed
Onur, OA, Schlaepfer, TE, Kukolja, J, Bauer, A, Jeung, H, Patin, A, Otte, DM, Shah, NJ, Maier, W, Kendrick, KM, Fink, GR, Hurlemann, R (2010). The N-methyl-D-aspartate receptor co-agonist D-cycloserine facilitates declarative learning and hippocampal activity in humans. Biological Psychiatry 67, 1205–1211.CrossRefGoogle ScholarPubMed
Papps, BP, Shajahan, PM, Ebmeier, KP, O'Carroll, RE (2002). The effects of noradrenergic re-uptake inhibition on memory encoding in man. Psychopharmacology (Berlin) 159, 311–318.CrossRefGoogle ScholarPubMed
Penny, WD, Holmes, AP (2003). Random effects analysis. In Human Brain Function (ed. Frackowiak, R. S. J., Friston, K. J., Frith, C. D., Dolan, R. J., Price, C. J., Ashburner, J. and Penny, W. D.), pp. 843–850. Academic Press: San Diego.Google Scholar
Phelps, EA (2004). Human emotion and memory: interactions of the amygdala and hippocampal complex. Current Opinion in Neurobiology 14, 198–202.CrossRefGoogle ScholarPubMed
Putman, P, Hermans, EJ, Koppeschaar, H, van Schijndel, A, van Honk, J (2007). A single administration of cortisol acutely reduces preconscious attention for fear in anxious young men. Psychoneuroendocrinology 32, 793–802.CrossRefGoogle ScholarPubMed
Quirarte, GL, Roozendaal, B, McGaugh, JL (1997). Glucocorticoid enhancement of memory storage involves noradrenergic activation in the basolateral amygdala. Proceedings of the National Academy of Sciences USA 94, 14048–14053.CrossRefGoogle ScholarPubMed
Rauch, SL, Whalen, PJ, Shin, LM, McInerney, SC, Macklin, ML, Lasko, NB, Orr, SP, Pitman, RK (2000). Exaggerated amygdala response to masked facial stimuli in posttraumatic stress disorder: a functional MRI study. Biological Psychiatry 47, 769–776.CrossRefGoogle ScholarPubMed
Richardson, MP, Strange, BA, Dolan, RJ (2004). Encoding of emotional memories depends on amygdala and hippocampus and their interactions. Nature Neuroscience 7, 278–285.CrossRefGoogle ScholarPubMed
Roozendaal, B, McEwen, BS, Chattarji, S (2009). Stress, memory and the amygdala. Nature Reviews Neuroscience 10, 423–433.CrossRefGoogle ScholarPubMed
Roozendaal, B, Okuda, S, van der Zee, EA, McGaugh, JL (2006). Glucocorticoid enhancement of memory requires arousal-induced noradrenergic activation in the basolateral amygdala. Proceedings of the National Academy of Sciences USA 103, 6741–6746.CrossRefGoogle ScholarPubMed
Rosenkranz, JA, Venheim, ER, Padival, M (2010). Chronic stress causes amygdala hyperexcitability in rodents. Biological Psychiatry 67, 1128–1136.CrossRefGoogle ScholarPubMed
Scates, AC, Doraiswamy, PM (2000). Reboxetine: a selective norepinephrine reuptake inhibitor for the treatment of depression. Annals of Pharmacotherapy 34, 1302–1312.CrossRefGoogle ScholarPubMed
Shin, LM, Wright, CI, Cannistraro, PA, Wedig, MM, McMullin, K, Martis, B, Macklin, ML, Lasko, NB, Cavanagh, SR, Krangel, TS, Orr, SP, Pitman, RK, Whalen, PJ, Rauch, SL (2005). A functional magnetic resonance imaging study of amygdala and medial prefrontal cortex responses to overtly presented fearful faces in posttraumatic stress disorder. Archives of General Psychiatry 62, 273–281.CrossRefGoogle ScholarPubMed
Soravia, LM, Heinrichs, M, Aerni, A, Maroni, C, Schelling, G, Ehlert, U, Roozendaal, B, de Quervain, DJ (2006). Glucocorticoids reduce phobic fear in humans. Proceedings of the National Academy of Sciences USA 103, 5585–5590.CrossRefGoogle ScholarPubMed
Stanislaw, H, Todorov, N (1999). Calculation of signal detection theory measures. Behavior Research Methods, Instruments and Computers 31, 137–149.CrossRefGoogle ScholarPubMed
Strange, BA, Dolan, RJ (2004). Beta-adrenergic modulation of emotional memory-evoked human amygdala and hippocampal responses. Proceedings of the National Academy of Sciences USA 101, 11454–11458.CrossRefGoogle ScholarPubMed
van Stegeren, AH, Goekoop, R, Everaerd, W, Scheltens, P, Barkhof, F, Kuijer, JP, Rombouts, SA (2005). Noradrenaline mediates amygdala activation in men and women during encoding of emotional material. Neuroimage 24, 898–909.CrossRefGoogle ScholarPubMed
van Stegeren, AH, Roozendaal, B, Kindt, M, Wolf, OT, Joels, M (2010). Interacting noradrenergic and corticosteroid systems shift human brain activation patterns during encoding. Neurobiology of Learning and Memory 93, 56–65.CrossRefGoogle ScholarPubMed
van Stegeren, AH, Wolf, OT, Everaerd, W, Scheltens, P, Barkhof, F, Rombouts, SA (2007). Endogenous cortisol level interacts with noradrenergic activation in the human amygdala. Neurobiology of Learning and Memory 87, 57–66.CrossRefGoogle ScholarPubMed
Worsley, KJ, Marrett, S, Neelin, P, Vandal, AC, Friston, KJ, Evans, AC (1996). A unified statistical approach for determining significant signals in images of cerebral activation. Human Brain Mapping 4, 58–74.3.0.CO;2-O>CrossRefGoogle ScholarPubMed
Yamamoto, S, Morinobu, S, Takei, S, Fuchikami, M, Matsuki, A, Yamawaki, S, Liberzon, I (2009). Single prolonged stress: toward an animal model of posttraumatic stress disorder. Depression and Anxiety 26, 1110–1117.CrossRefGoogle ScholarPubMed
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