title: Glucocorticoids mediate stress-induced impairment of retrieval of stimulus-response memory.
abstract: Acute stress and elevated glucocorticoid hormone levels are well known to impair the retrieval of hippocampus-dependent 'declarative' memory. Recent findings suggest that stress might also impair the retrieval of non-hippocampal memories. In particular, stress shortly before retention testing was shown to impair the retrieval of striatal stimulus-response associations in humans. However, the mechanism underlying this stress-induced retrieval impairment of non-hippocampal stimulus-response memory remains elusive. In the present study, we investigated whether an acute elevation in glucocorticoid levels mediates the impairing effects of stress on retrieval of stimulus-response memory. Male Sprague-Dawley rats were trained on a stimulus-response task in an eight-arm radial maze until they learned to associate a stimulus, i.e., cue, with a food reward in one of the arms. Twenty-four hours after successful acquisition, they received a systemic injection of vehicle, corticosterone (1mg/kg), the corticosterone-synthesis inhibitor metyrapone (35mg/kg) or were left untreated 1h before retention testing. We found that the corticosterone injection impaired the retrieval of stimulus-response memory. We further found that the systemic injection procedure per se was stressful as the vehicle administration also increased plasma corticosterone levels and impaired the retrieval of stimulus-response memory. However, memory retrieval was not impaired when rats were tested 2min after the systemic vehicle injection, before any stress-induced elevation in corticosterone levels had occurred. Moreover, metyrapone treatment blocked the effect of injection stress on both plasma corticosterone levels and memory retrieval impairment, indicating that the endogenous corticosterone response mediates the stress-induced memory retrieval impairment. None of the treatments affected rats' locomotor activity or motivation to search for the food reward within the maze. These findings show that stress may affect memory processes beyond the hippocampus and that these stress effects are due to the action of glucocorticoids.
authors.affiliation: Department of Cognitive Neuroscience, Radboud University Medical Center, 6500 HB Nijmegen, The Netherlands; Donders Institute for Brain, Cognition and Behavior, Radboud University Nijmegen, 6525 EZ Nijmegen, The Netherlands. Electronic address: Piray.Atsak@radboudumc.nl.
authors.forename: Piray
authors.initials: P
authors.lastname: Atsak
authors.affiliation: Department of Cognitive Neuroscience, Radboud University Medical Center, 6500 HB Nijmegen, The Netherlands; Institute of Cognitive Neuroscience, Department of Cognitive Psychology, Ruhr-University Bochum, 44780 Bochum, Germany.
authors.forename: Friederike M
authors.initials: FM
authors.lastname: Guenzel
authors.affiliation: Department of Cognitive Neuroscience, Radboud University Medical Center, 6500 HB Nijmegen, The Netherlands; Department of Biophysics, Faculty of Medicine, Akdeniz University, Arapsuyu, 07070 Antalya, Turkey.
authors.forename: Deniz
authors.initials: D
authors.lastname: Kantar-Gok
authors.affiliation: Department of Endocrinology and Metabolism, Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, 2300 RA Leiden, The Netherlands.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Zalachoras
authors.affiliation: Department of Biophysics, Faculty of Medicine, Akdeniz University, Arapsuyu, 07070 Antalya, Turkey.
authors.forename: Piraye
authors.initials: P
authors.lastname: Yargicoglu
authors.affiliation: Department of Endocrinology and Metabolism, Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, 2300 RA Leiden, The Netherlands.
authors.forename: Onno C
authors.initials: OC
authors.lastname: Meijer
authors.affiliation: Departamento de Neurobiología Conductual y Cognitiva, Instituto de Neurobiología, Universidad Nacional Autónoma de México, Campus Juriquilla, Querétaro 76230, Mexico.
authors.forename: Gina L
authors.initials: GL
authors.lastname: Quirarte
authors.affiliation: Institute of Cognitive Neuroscience, Department of Cognitive Psychology, Ruhr-University Bochum, 44780 Bochum, Germany.
authors.forename: Oliver T
authors.initials: OT
authors.lastname: Wolf
authors.affiliation: Department of Cognitive Psychology, University of Hamburg, 20146 Hamburg, Germany.
authors.forename: Lars
authors.initials: L
authors.lastname: Schwabe
authors.affiliation: Department of Cognitive Neuroscience, Radboud University Medical Center, 6500 HB Nijmegen, The Netherlands; Donders Institute for Brain, Cognition and Behavior, Radboud University Nijmegen, 6525 EZ Nijmegen, The Netherlands.
authors.forename: Benno
authors.initials: B
authors.lastname: Roozendaal
mesh_terms: D000818:Animals; D003345:Corticosterone / Q000097:blood*; D007267:Injections / Q000523:psychology*; D008124:Locomotion / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D011939:Mental Recall / Q000187:drug effects*; D008797:Metyrapone / Q000494:pharmacology*; D009042:Motivation / Q000187:drug effects; D051381:Rats; D013315:Stress, Psychological / Q000097:blood* / Q000523:psychology*
chemical_list: D003345:Corticosterone; D008797:Metyrapone
keywords: Glucocorticoids; Metyrapone; Retrieval; Stimulus-response memory; Stress; Striatum