Advertisement

Mineralocorticoid Receptor Blockade Prevents Stress-Induced Modulation of Multiple Memory Systems in the Human Brain

      Background

      Accumulating evidence suggests that stress may orchestrate the engagement of multiple memory systems in the brain. In particular, stress is thought to favor dorsal striatum-dependent procedural over hippocampus-dependent declarative memory. However, the neuroendocrine mechanisms underlying these modulatory effects of stress remain elusive, especially in humans. Here, we targeted the role of the mineralocorticoid receptor (MR) in the stress-induced modulation of dorsal striatal and hippocampal memory systems in the human brain using a combination of event-related functional magnetic resonance imaging and pharmacologic blockade of the MR.

      Methods

      Eighty healthy participants received the MR antagonist spironolactone (300 mg) or a placebo and underwent a stressor or control manipulation before they performed, in the scanner, a classification task that can be supported by the hippocampus and the dorsal striatum.

      Results

      Stress after placebo did not affect learning performance but reduced explicit task knowledge and led to a relative increase in the use of more procedural learning strategies. At the neural level, stress promoted striatum-based learning at the expense of hippocampus-based learning. Functional connectivity analyses showed that this shift was associated with altered coupling of the amygdala with the hippocampus and dorsal striatum. Mineralocorticoid receptor blockade before stress prevented the stress-induced shift toward dorsal striatal procedural learning, same as the stress-induced alterations of amygdala connectivity with hippocampus and dorsal striatum, but resulted in significantly impaired performance.

      Conclusions

      Our findings indicate that the stress-induced shift from hippocampal to dorsal striatal memory systems is mediated by the amygdala, required to preserve performance after stress, and dependent on the MR.

      Key Words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Biological Psychiatry
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Diamond D.M.
        • Campbell A.M.
        • Park C.R.
        • Halonen J.
        • Zoladz P.R.
        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 Plast. 2007; 2007: 60803
        • Schwabe L.
        • Joëls M.
        • Roozendaal B.
        • Wolf O.T.
        • Oitzl M.S.
        Stress effects on memory: An update and integration.
        Neurosci Biobehav Rev. 2012; 36: 1740-1749
        • Roozendaal B.
        • McEwen B.S.
        • Chattarji S.
        Stress, memory and the amygdala.
        Nat Rev Neurosci. 2009; 10: 423-433
        • Buchanan T.W.
        • Lovallo W.R.
        Enhanced memory for emotional material following stress-level cortisol treatment in humans.
        Psychoneuroendocrinology. 2001; 26: 307-317
        • de Quervain D.J.
        • Aerni A.
        • Schelling G.
        • Roozendaal B.
        Glucocorticoids and the regulation of memory in health and disease.
        Front Neuroendocrinol. 2009; 30: 358-370
        • de Quervain D.J.
        • Roozendaal B.
        • McGaugh J.L.
        Stress and glucocorticoids impair retrieval of long-term spatial memory.
        Nature. 1998; 394: 787-790
        • Reul J.M.
        • de Kloet E.R.
        Two receptor systems for corticosterone in rat brain: Microdistribution and differential occupation.
        Endocrinology. 1985; 117: 2505-2511
        • de Kloet E.R.
        • Joels M.
        • Holsboer F.
        Stress and the brain: From adaptation to disease.
        Nat Rev Neurosci. 2005; 6: 463-475
        • Barsegyan A.
        • Mackenzie S.M.
        • Kurose B.D.
        • McGaugh J.L.
        • Roozendaal B.
        Glucocorticoids in the prefrontal cortex enhance memory consolidation and impair working memory by a common neural mechanism.
        Proc Natl Acad Sci U S A. 2010; 107: 16655-16660
        • Oitzl M.S.
        • de Kloet E.R.
        Selective corticosteroid antagonists modulate specific aspects of spatial orientation learning.
        Behav Neurosci. 1992; 106: 62-71
        • de Quervain D.J.
        • Henke K.
        • Aerni A.
        • Treyer V.
        • McGaugh J.L.
        • Berthold T.
        • et al.
        Glucocorticoid-induced impairment of declarative memory retrieval is associated with reduced blood flow in the medial temporal lobe.
        Eur J Neurosci. 2003; 17: 1296-1302
        • Diamond D.M.
        • Campbell A.M.
        • Park C.R.
        • Woodson J.C.
        • Conrad C.D.
        • Bachstetter A.D.
        • Mervis R.F.
        Influence of predator stress on the consolidation versus retrieval of the long-term spatial memory and hippocampal spinogenesis.
        Hippocampus. 2006; 16: 571-576
        • Payne J.D.
        • Jackson E.D.
        • Hoscheidt S.
        • Ryan L.
        • Jacobs W.J.
        • Nadel L.
        Stress administered prior to encoding impairs neutral but enhances emotional long-term episodic memories.
        Learn Mem. 2007; 14: 861-868
        • Lupien S.
        • McEwen B.S.
        The acute effects of corticosteroids on cognition: Integration of animal and human model studies.
        Brain Res Brain Res Rev. 1997; 24: 1-27
        • McEwen B.S.
        Stress and hippocampal plasticity.
        Annu Rev Neurosci. 1999; 22: 105-122
        • Schwabe L.
        • Wolf O.T.
        Stress and multiple memory systems: From ‘thinking’ to ‘doing’.
        Trends Cogn Sci. 2013; 17: 60-68
        • Schwabe L.
        • Wolf O.T.
        • Oitzl M.S.
        Memory formation under stress: Quantity and quality.
        Neurosci Biobehav Rev. 2010; 34: 584-591
        • Packard M.G.
        • Goodman J.
        Emotional arousal and multiple memory systems in the mammalian brain.
        Front Behav Neurosci. 2012; 6: 1-9
        • Schwabe L.
        • Oitzl M.S.
        • Philippsen C.
        • Böhringer A.
        • Richter S.
        • Wippich W.
        • Schachinger H.
        Stress modulates the use of spatial and stimulus-response learning strategies in humans.
        Learn Mem. 2007; 14: 109-116
        • Kim J.
        • Lee H.
        • Han J.
        • Packard M.G.
        Amygdala is critical for stress-induced modulation of hippocampal long-term potentiation and learning.
        J Neurosci. 2001; 21: 5222-5228
        • Packard M.G.
        • Wingard J.C.
        Amygdala and “emotional” modulation of the relative use of multiple memory systems.
        Neurobiol Learn Mem. 2004; 82: 243-252
        • VanElzakker M.B.
        • Zoladz P.R.
        • Thompson V.M.
        • Park C.R.
        • Halonen J.D.
        • Spencer R.L.
        • Diamond D.M.
        Influence of pre-training predator stress on the expression of c-fos mRNA in the hippocampus, amygdala, and striatum following long-term spatial memory retrieval.
        Front Behav Neurosci. 2011; 5: 1-13
        • Schwabe L.
        • Dalm S.
        • Schachinger H.
        • Oitzl M.S.
        Chronic stress modulates the use of spatial and stimulus-response learning strategies in mice and man.
        Neurobiol Learn Mem. 2008; 90: 495-503
        • Schwabe L.
        • Wolf O.T.
        Stress modulates the engagement of multiple memory systems in classification learning.
        J Neurosci. 2012; 32: 11042-11049
        • Packard M.G.
        Anxiety, cognition, and habit: A multiple memory systems perspective.
        Brain Res. 2009; 1293: 121-128
        • Buckley T.C.
        • Blanchard E.B.
        • Neill W.T.
        Information processing and PTSD: A review of the empirical literature.
        Clin Psychol Rev. 2000; 20: 1041-1065
        • Liberzon I.
        • Taylor S.F.
        • Amdur R.
        • Jung T.D.
        • Chamberlain K.R.
        • Minoshima S.
        • et al.
        Brain activation in PTSD in response to trauma-related stimuli.
        Biol Psychiatry. 1999; 45: 817-826
        • Schwabe L.
        • Schächinger H.
        • de Kloet E.R.
        • Oitzl M.S.
        Corticosteroids operate as switch between memory systems.
        J Cogn Neurosci. 2010; 22: 1362-1372
        • Schwabe L.
        • Haddad L.
        • Schachinger H.
        HPA axis activation by a socially evaluated cold pressor test.
        Psychoneuroendocrinology. 2008; 33: 890-895
        • Foerde K.
        • Knowlton B.J.
        • Poldrack R.A.
        Modulation of competing memory systems by distraction.
        Proc Natl Acad Sci U S A. 2006; 103: 11778-11783
        • Knowlton B.J.
        • Mangels J.A.
        • Squire L.R.
        A neostriatal habit learning system in humans.
        Science. 1996; 273: 1399-1402
        • Poldrack R.A.
        • Clark J.
        • Paré-Blagoev E.J.
        • Shohamy D.
        • Creso Moyano J.
        • Myers C.
        • Gluck M.A.
        Interactive memory systems in the human brain.
        Nature. 2001; 414: 546-550
        • Cornelisse S.
        • Joels M.
        • Smeets T.
        A randomized trial on mineralocorticoid receptor blockade in men: Effects on stress responses, selective attention, and memory.
        Neuropsychopharmacology. 2011; 36: 2720-2728
        • Knowlton B.J.
        • Squire L.R.
        • Gluck M.A.
        Probabilistic classification learning in amnesia.
        Learn Mem. 1994; 1: 106-120
        • Gluck M.A.
        • Shohamy D.
        • Myers C.E.
        How do people solve the “weather prediction” task?: Individual variability in strategies for probabilistic category learning.
        Learn Mem. 2002; 9: 408-418
        • Lagnado D.A.
        • Newell B.R.
        • Kahan S.
        • Shanks D.R.
        Insight and strategy in multiple-cue learning.
        J Exp Psychol Gen. 2006; 135: 162-183
        • Thomas L.A.
        • LaBar K.S.
        Fear relevancy, strategy use, and probabilistic learning of cue-outcome associations.
        Learn Mem. 2008; 15: 777-784
        • Kloet E.R.
        • deRijk R.
        Signaling pathways in brain involved in predisposition and pathogenesis of stress-related disease: Genetic and kinetic factors affecting the MR/GR balance.
        Ann N Y Acad Sci. 2004; 1032 (de): 14-34
        • Otte C.
        • Moritz S.
        • Yassouridis A.
        • Koop M.
        • Madrischewski A.M.
        • Wiedemann K.
        • Kellner M.
        Blockade of the mineralocorticoid receptor in healthy men: Effects on experimentally induced panic symptoms, stress hormones, and cognition.
        Neuropsychopharmacology. 2007; 32: 232-238
        • Pruessner J.C.
        • Kirschbaum C.
        • Meinlschmid G.
        • Hellhammer D.H.
        Two formulas for computation of the area under the curve represent measures of total hormone concentration versus time-dependent change.
        Psychoneuroendocrinolgy. 2003; 28: 916-931
        • van den Berg D.T.
        • de Jong W.
        • de Kloet E.R.
        Mineralocorticoid antagonist inhibits stress-induced blood pressure response after repeated daily warming.
        Am J Physiol. 1994; 267: E921-E926
        • Shohamy D.
        • Myers C.E.
        • Grossman S.
        • Sage J.
        • Gluck M.A.
        • Poldrack R.A.
        Cortico-striatal contributions to feedback-based learning: Converging data from neuroimaging and neuropsychology.
        Brain. 2004; 127: 851-859
        • Roozendaal B.
        • Okuda S.
        • Van der Zee E.A.
        • McGaugh J.L.
        Glucocorticoid enhancement of memory requires arousal-induced noradrenergic activation in the basolateral amygdala.
        Proc Natl Acad Sci U S A. 2006; 103: 6741-6746
        • Groeneweg F.L.
        • Karst H.
        • De Kloet E.R.
        • Joels M.
        Mineralocorticoid and glucocorticoid receptors at the neuronal membrane, regulators of nongenomic corticosteroid signalling.
        Mol Cell Endocrinol. 2012; 350: 299-309
        • Joels M.
        • Karst H.
        • DeRijk R.
        • De Kloet E.R.
        The coming out of the brain mineralocorticoid receptor.
        Trends Neurosci. 2008; 31: 1-7
        • Heuser I.
        • Deuschle M.
        • Weber B.
        • Stalla G.K.
        • Holsboer F.
        Increased activity of the hypothalamus-pituitary-adrenal system after treatment with the mineralocorticoid receptor antagonist spironolactone.
        Psychoneuroendocrinology. 2000; 25: 513-518
        • McGaugh J.L.
        Memory consolidation and amygdala: A systems perspective.
        Trends Neurosci. 2002; 25: 456-461
        • Roozendaal B.
        • Okuda S.
        • De Quervain D.J.
        • McGaugh J.L.
        Glucocorticoids interact with emotion-induced noradrenergic activation in influencing different memory functions.
        Neuroscience. 2006; 138: 901-910
        • ter Horst J.P.
        • van der Mark M.H.
        • Arp M.
        • Berger S.
        • de Kloet E.R.
        • Oitzl M.S.
        Stress or no stress: Mineralocorticoid receptors in the forebrain regulate behavioral adaptation.
        Neurobiol Learn Mem. 2012; 98: 33-40
        • Roozendaal B.
        • Hernandez A.
        • Cabrera S.M.
        • Hagewood R.
        • Malvaez M.
        • Stefanko D.P.
        • et al.
        Membrane-associated glucocorticoid activity is necessary for modulation of long-term memory via chromatin modification.
        J Neurosci. 2010; 30: 5037-5046
        • Schroeder J.P.
        • Wingard J.C.
        • Packard M.G.
        Post-training reversible inactivation of hippocampus reveals interference between memory systems.
        Hippocampus. 2002; 12: 280-284
        • Quirarte G.L.
        • Roozendaal B.
        • McGaugh J.L.
        Glucocorticoid enhancement of memory storage involves noradrenergic activation in the basolateral amygdala.
        Proc Natl Acad Sci U S A. 1997; 94: 14048-14053
        • Roozendaal B.
        • McGaugh J.L.
        Basolateral amygdala lesions block the memory-enhancing effect of glucocorticoid administration in the dorsal hippocampus of rats.
        Eur J Neurosci. 1997; 9: 76-83
        • Packard M.G.
        • Teather L.A.
        Amygdala modulation of multiple memory systems: Hippocampus and caudate-putamen.
        Neurobiol Learn Mem. 1998; 69: 163-203
        • Karst H.
        • Berger S.
        • Erdmann G.
        • Schütz G.
        • Joels M.
        Metaplasticity of amygdalar responses to the stress hormone corticosterone.
        Proc Natl Acad Sci U S A. 2010; 107: 14449-14454
        • Wolf O.T.
        The influence of stress hormones on emotional memory: Relevance for psychopathology.
        Acta Psychol (Amst). 2008; 127: 513-531
        • Pitman R.K.
        Post-traumatic stress disorder, hormones, and memory.
        Biol Psychiatry. 1989; 26: 221-223
        • Goodman J.
        • Leong K.C.
        • Packard M.G.
        Emotional modulation of multiple memory systems: Implications for the neurobiology of post-traumatic stress disorder.
        Rev Neurosci. 2012; 23: 627-643
        • Born J.
        • de Kloet E.R.
        • Wenz H.
        • Kern W.
        • Fehm H.L.
        Gluco- and antimineralocorticoid effects on human sleep: A role of central corticosteroid receptors.
        Am J Physiol. 1991; 260: E183-E188
        • Belanoff J.K.
        • Rothschild A.J.
        • Cassidy F.
        • DeBattista C.
        • Baulieu E.E.
        • Schold C.
        • Schatzberg A.F.
        An open label trial of C-1073 (mifepristone) for psychotic major depression.
        Biol Psychiatry. 2002; 52: 386-392
        • DeBattista C.
        • Belanoff J.K.
        The use of mifepristone in the treatment of neuropsychiatric-disorders.
        Trends Endocrinol Metab. 2006; 17: 117-121
        • de Kloet E.R.
        • Vreugdenhil E.
        • Oitzl M.S.
        • Joels M.
        Brain corticosteroid receptor balance in health and disease.
        Endocr Rev. 1998; 19: 269-301
        • ter Horst J.P.
        • Kentrop J.
        • de Kloet E.R.
        • Oitzl M.S.
        Stress and estrous cycle affect strategy but not performance of female C57BL/6J mice.
        Behav Brain Res. 2013; 241: 92-95