title: Stimulation of the noradrenergic system during memory formation impairs extinction learning but not the disruption of reconsolidation.
abstract: The noradrenergic system plays a critical role in the 'consolidation' of emotional memory. If we are to target 'reconsolidation' in patients with anxiety disorders, the noradrenergic strengthening of fear memory should not impair the disruption of reconsolidation. In Experiment I, we addressed this issue using a differential fear conditioning procedure allowing selective reactivation of one of two fear associations. First, we strengthened fear memory by administering an α(2)-adrenergic receptor antagonist (ie, yohimbine HCl; double-blind placebo-controlled study) 30 min before acquisition (time for peak value yohimbine HCl <1 h). Next, the reconsolidation of one of the fear associations was manipulated by administering a β-adrenergic receptor antagonist (ie, propranolol HCl) 90 min before its selective reactivation (time for peak value propranolol HCl <2 h). In Experiment II, we administered propranolol HCl after reactivation of the memory to rule out a possible effect of the pharmacological manipulation on the memory retrieval itself. The excessive release of noradrenaline during memory formation not only delayed the process of extinction 48 h later, but also triggered broader fear generalization. Yet, the β-adrenergic receptor blocker during reconsolidation selectively 'neutralized' the fear-arousing aspects of the noradrenergic-strengthened memory and undermined the generalization of fear. We observed a similar reduction in fear responding when propranolol HCl was administered after reactivation of the memory. The present findings demonstrate the involvement of noradrenergic modulation in the formation as well as generalization of human fear memory. Given that the noradrenergic strengthening of fear memory impaired extinction learning but not the disruption of reconsolidation, our findings may have implications for the treatment of anxiety disorders.
authors.affiliation: Department of Clinical Psychology, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Marieke
authors.initials: M
authors.lastname: Soeter
authors.forename: Merel
authors.initials: M
authors.lastname: Kindt
mesh_terms: D000293:Adolescent; D058669:Adrenergic alpha-2 Receptor Antagonists / Q000009:adverse effects; D000319:Adrenergic beta-Antagonists / Q000009:adverse effects; D000328:Adult; D000704:Analysis of Variance; D001794:Blood Pressure / Q000187:drug effects; D003214:Conditioning, Classical / Q000187:drug effects* / Q000502:physiology; D004311:Double-Blind Method; D004558:Electric Stimulation / Q000009:adverse effects; D005108:Extinction, Psychological / Q000187:drug effects*; D005239:Fear; D005260:Female; D005712:Galvanic Skin Response / Q000187:drug effects; D006801:Humans; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced*; D009638:Norepinephrine / Q000502:physiology*; D011433:Propranolol / Q000009:adverse effects; D055291:Salivary alpha-Amylases / Q000378:metabolism; D013997:Time Factors; D015016:Yohimbine / Q000009:adverse effects; D055815:Young Adult
chemical_list: D058669:Adrenergic alpha-2 Receptor Antagonists; D000319:Adrenergic beta-Antagonists; D015016:Yohimbine; D011433:Propranolol; D055291:Salivary alpha-Amylases; D009638:Norepinephrine