title: Emotional memory can be persistently weakened by suppressing cortisol during retrieval.
abstract: Cortisol's effects on memory follow an inverted U-shaped function such that memory retrieval is impaired with very low concentrations, presumably due to insufficient activation of high-affine mineralocorticoid receptors (MR), or with very high concentrations, due to predominant low-affine glucocorticoid receptor (GR) activation. Through corresponding changes in re-encoding, the retrieval effect of cortisol might translate into a persistent change of the retrieved memory. We tested whether partial suppression of morning cortisol synthesis by metyrapone, leading to intermediate, circadian nadir-like levels with presumed predominant MR activation, improves retrieval, particularly of emotional memory, and persistently changes the memory. In a randomized, placebo-controlled, double-blind, within-subject cross-over design, 18 men were orally administered metyrapone (1g) vs. placebo at 4:00 AM to suppress the morning cortisol rise. Retrieval of emotional and neutral texts and pictures (learned 3 days earlier) was assessed 4h after substance administration and a second time one week later. Metyrapone suppressed endogenous cortisol release to circadian nadir-equivalent levels at the time of retrieval testing. Contrary to our expectations, metyrapone significantly impaired free recall of emotional texts (p<.05), whereas retrieval of neutral texts or pictures remained unaffected. One week later, participants still showed lower memory for emotional texts in the metyrapone than placebo condition (p<.05). Our finding that suppressing morning cortisol to nadir-like concentrations not only impairs acute retrieval, but also persistently weakens emotional memories corroborates the concept that retrieval effects of cortisol produce persistent memory changes, possibly by affecting re-encoding.
authors: Department of Neurosciences, University of Geneva, Campus Biotech, CP 60, 1211 Geneva 20, Geneva, Switzerland. Electronic address: ulrike.rimmele@unige.ch.
authors: Ulrike
authors: U
authors: Rimmele
authors: Department of Medical Psychology and Behavioral Neurobiology, University of Tübingen, Tübingen Otfried-Müller-Str. 25, 72076 Tübingen, Germany.
authors: Luciana
authors: L
authors: Besedovsky
authors: Department of Medical Psychology and Behavioral Neurobiology, University of Tübingen, Tübingen Otfried-Müller-Str. 25, 72076 Tübingen, Germany; Department of Neuroendocrinology, University of Lübeck, Ratzeburger Allee 160, Lübeck, Germany.
authors: Tanja
authors: T
authors: Lange
authors: Department of Medical Psychology and Behavioral Neurobiology, University of Tübingen, Tübingen Otfried-Müller-Str. 25, 72076 Tübingen, Germany; Center for Integrative Neuroscience, University of Tübingen, FIN Bau, Otfried-Müller-Str. 25, 72076 Tübingen, Germany; German Center for Diabetes Research, Tübingen, Germany; Institute for Diabetes Research and Metabolic Diseases of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany.
authors: Jan
authors: J
authors: Born
mesh_terms: D000328:Adult; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004644:Emotions / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D006854:Hydrocortisone / Q000502:physiology*; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D011939:Mental Recall / Q000187:drug effects / Q000502:physiology*; D008797:Metyrapone / Q000008:administration & dosage; D055815:Young Adult
chemical_list: D006854:Hydrocortisone; D008797:Metyrapone
keywords: Cortisol; Memory; Metyrapone; Recall; Retrieval; Suppression