Noradrenergic stimulation increases fear memory expression
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Noradrenergic stimulation increases fear memory expression. / Kausche, Franziska Magdalena; Zerbes, Gundula; Kampermann, Lea; Müller, Jana Christina; Wiedemann, Klaus; Büchel, Christian; Schwabe, Lars.
in: EUR NEUROPSYCHOPHARM, Jahrgang 43, 02.2021, S. 71-81.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - Noradrenergic stimulation increases fear memory expression
AU - Kausche, Franziska Magdalena
AU - Zerbes, Gundula
AU - Kampermann, Lea
AU - Müller, Jana Christina
AU - Wiedemann, Klaus
AU - Büchel, Christian
AU - Schwabe, Lars
N1 - Copyright © 2020. Published by Elsevier B.V.
PY - 2021/2
Y1 - 2021/2
N2 - Fear responses are typically not limited to the actual threatening stimulus but generalize to other stimuli resembling the threatening stimulus. Although this fear generalization is generally adaptive, fear overgeneralization is maladaptive and assumed to contribute to anxiety disorders. Despite the clinical relevance of fear (over)generalization, how the extent of fear generalization is modulated remains not well understood. Based on the known effects of stress on learning and memory, we tested here the impact of major stress mediators, glucocorticoids and noradrenergic arousal, on fear generalization. In a laboratory-based, placebo-controlled, double-blind, between-subject design, 125 healthy participants first underwent a fear conditioning procedure. About 24 h later, participants received orally either a placebo, hydrocortisone, the α2-adrenoceptor antagonist yohimbine, leading to increased noradrenergic stimulation, or both drugs before a test of fear generalization. Skin conductance responses as well as explicit rating data revealed that yohimbine intake led to enhanced fear memory expression, i.e. an enhanced responding to the CS+ but not to stimuli resembling the CS+. Moreover, neither enhanced safety learning nor a mere enhancement of perceptual discrimination ability could explain this result. In contrast to yohimbine, hydrocortisone had no significant effect on fear memory. These findings suggest that noradrenergic arousal strengthens fear memory expression and have important implications for mental disorders in which the overgeneralization of conditioned fear is prominent.
AB - Fear responses are typically not limited to the actual threatening stimulus but generalize to other stimuli resembling the threatening stimulus. Although this fear generalization is generally adaptive, fear overgeneralization is maladaptive and assumed to contribute to anxiety disorders. Despite the clinical relevance of fear (over)generalization, how the extent of fear generalization is modulated remains not well understood. Based on the known effects of stress on learning and memory, we tested here the impact of major stress mediators, glucocorticoids and noradrenergic arousal, on fear generalization. In a laboratory-based, placebo-controlled, double-blind, between-subject design, 125 healthy participants first underwent a fear conditioning procedure. About 24 h later, participants received orally either a placebo, hydrocortisone, the α2-adrenoceptor antagonist yohimbine, leading to increased noradrenergic stimulation, or both drugs before a test of fear generalization. Skin conductance responses as well as explicit rating data revealed that yohimbine intake led to enhanced fear memory expression, i.e. an enhanced responding to the CS+ but not to stimuli resembling the CS+. Moreover, neither enhanced safety learning nor a mere enhancement of perceptual discrimination ability could explain this result. In contrast to yohimbine, hydrocortisone had no significant effect on fear memory. These findings suggest that noradrenergic arousal strengthens fear memory expression and have important implications for mental disorders in which the overgeneralization of conditioned fear is prominent.
U2 - 10.1016/j.euroneuro.2020.11.015
DO - 10.1016/j.euroneuro.2020.11.015
M3 - SCORING: Journal article
C2 - 33358539
VL - 43
SP - 71
EP - 81
JO - EUR NEUROPSYCHOPHARM
JF - EUR NEUROPSYCHOPHARM
SN - 0924-977X
ER -