title: Noradrenergic Stimulation Impairs Memory Generalization in Women.
abstract: Memory generalization is essential for adaptive decision-making and action. Our ability to generalize across past experiences relies on medial-temporal lobe structures, known to be highly sensitive to stress. Recent evidence suggests that stressful events may indeed interfere with memory generalization. Yet, the mechanisms involved in this generalization impairment are unknown. We tested here whether a pharmacological elevation of major stress mediators-noradrenaline and glucocorticoids-is sufficient to disrupt memory generalization. In a double-blind, placebo-controlled design, healthy men and women received orally a placebo, hydrocortisone, the α2-adrenoceptor antagonist yohimbine that leads to increased noradrenergic stimulation, or both drugs, before they completed an associative learning task probing memory generalization. Drugs left learning performance intact. Yohimbine, however, led to a striking generalization impairment in women, but not in men. Hydrocortisone, in turn, had no effect on memory generalization, neither in men nor in women. The present findings indicate that increased noradrenergic activity, but not cortisol, is sufficient to disrupt memory generalization in a sex-specific manner, with relevant implications for stress-related mental disorders characterized by generalization deficits.
authors.affiliation: 1 University of Hamburg.
authors.forename: Lisa Marieke
authors.initials: LM
authors.lastname: Kluen
authors.affiliation: 2 University Clinic Hamburg-Eppendorf.
authors.forename: Agorastos
authors.initials: A
authors.lastname: Agorastos
authors.affiliation: 2 University Clinic Hamburg-Eppendorf.
authors.forename: Klaus
authors.initials: K
authors.lastname: Wiedemann
authors.affiliation: 1 University of Hamburg.
authors.forename: Lars
authors.initials: L
authors.lastname: Schwabe
mesh_terms: D000284:Administration, Oral; D058669:Adrenergic alpha-2 Receptor Antagonists / Q000494:pharmacology*; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001245:Association Learning / Q000187:drug effects / Q000502:physiology; D004311:Double-Blind Method; D005260:Female; D005793:Generalization, Psychological / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D008297:Male; D008568:Memory / Q000187:drug effects* / Q000502:physiology*; D012727:Sex Characteristics; D015016:Yohimbine / Q000494:pharmacology; D055815:Young Adult
chemical_list: D058669:Adrenergic alpha-2 Receptor Antagonists; D000893:Anti-Inflammatory Agents; D015016:Yohimbine; D006854:Hydrocortisone