Disrupting reconsolidation: pharmacological and behavioral manipulations

Learn Mem. 2011 May 16;18(6):357-66. doi: 10.1101/lm.2148511. Print 2011 Jun.

Abstract

We previously demonstrated that disrupting reconsolidation by pharmacological manipulations "deleted" the emotional expression of a fear memory in humans. If we are to target reconsolidation in patients with anxiety disorders, the disruption of reconsolidation should produce content-limited modifications. At the same time, the fear-erasing effects should not be restricted to the feared cue itself considering that fear generalization is a main characteristic of anxiety disorders. In Experiment I and Experiment I(b), we addressed these issues using a within-subject differential startle fear conditioning paradigm and a test of fear generalization. In Experiment II, we tested whether a behavioral approach targeting the reconsolidation through extinction learning was also effective in weakening the original fear memory. A behavioral procedure is evidently preferred over drug manipulations provided that similar effects can be obtained. Here, the extinction procedure subsequent to retrieval did not "erase" the emotional expression of the fear memory as the retrieval techniques (i.e., reminder shocks and reacquisition) unveiled a return of the startle fear response to the fear-relevant stimuli. In contrast, β-adrenergic receptor blockade during reconsolidation selectively deleted the fear-arousing aspects of the memory (i.e., startle fear response) along with its category-related information. The pharmacological manipulation rendered the core memory trace too weak to observe fear generalization after successful reacquisition. Hence, relearning following the disruption of reconsolidation seems to be qualitatively different from initial learning. Our findings demonstrate that disrupting reconsolidation by pharmacological manipulations, although selective, undermines the generalization of fear, a key feature of anxiety disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adrenergic beta-Antagonists / adverse effects*
  • Adult
  • Analysis of Variance
  • Blood Pressure / drug effects
  • Conditioning, Classical / drug effects
  • Electric Stimulation / adverse effects
  • Extinction, Psychological / drug effects
  • Fear / drug effects
  • Female
  • Galvanic Skin Response / drug effects
  • Generalization, Psychological / drug effects
  • Humans
  • Male
  • Memory Disorders / chemically induced*
  • Memory Disorders / physiopathology*
  • Propranolol / adverse effects*
  • Psychiatric Status Rating Scales
  • Reflex, Startle / drug effects
  • Saliva / chemistry
  • Stress, Psychological / chemically induced
  • Young Adult
  • alpha-Amylases / metabolism

Substances

  • Adrenergic beta-Antagonists
  • Propranolol
  • alpha-Amylases