Neurobiological Dissociation of Retrieval and Reconsolidation of Cocaine-Associated Memory

J Neurosci. 2013 Jan 16;33(3):1271-81a. doi: 10.1523/JNEUROSCI.3463-12.2013.

Abstract

Drug use is provoked by the presentation of drug-associated cues, even following long periods of abstinence. Disruption of these learned associations would therefore limit relapse susceptibility. Drug-associated memories are susceptible to long-term disruption during retrieval and shortly after, during memory reconsolidation. Recent evidence reveals that retrieval and reconsolidation are dependent on β-adrenergic receptor (β-AR) activation. Despite this, whether retrieval and reconsolidation are dependent on identical or distinct neural mechanisms is unknown. The prelimbic medial prefrontal cortex (PL-mPFC) and basolateral amygdala (BLA) have been implicated in the expression and reconsolidation of associative memories. Therefore, we investigated the necessity of β-AR activation within the PL-mPFC and BLA for cocaine-associated memory retrieval and reconsolidation in rats. Before or immediately after a cocaine-induced conditioned place preference (CPP) retrieval trial, β-AR antagonists were infused into the PL-mPFC or BLA, followed by daily testing. PL-mPFC infusions before, but not after, a CPP trial disrupted CPP memory retrieval and induced a persistent deficit in retrieval during subsequent trials. In contrast, BLA β-AR blockade had no effect on initial CPP memory retrieval, but prevented CPP expression during subsequent trials indicative of reconsolidation disruption. Our results reveal a distinct dissociation between the neural mechanisms required for cocaine-associated memory retrieval and reconsolidation. Using patch-clamp electrophysiology, we also show that application of a β-AR antagonist prevents norepinephrine-induced potentiation of PL-mPFC pyramidal cell and γ-aminobutyric-acid (GABA) interneuron excitability. Thus, targeted β-AR blockade could induce long-term deficits in drug-associated memory retrieval by reducing neuronal excitability, providing a novel method of preventing cue-elicited drug seeking and relapse.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adrenergic beta-Antagonists / pharmacology
  • Amygdala / drug effects
  • Animals
  • Association Learning / drug effects*
  • Cocaine / administration & dosage*
  • Conditioning, Operant / drug effects*
  • Cues
  • Dopamine Uptake Inhibitors / administration & dosage*
  • Extinction, Psychological / drug effects
  • Male
  • Memory / drug effects*
  • Prefrontal Cortex / drug effects
  • Rats
  • Rats, Long-Evans

Substances

  • Adrenergic beta-Antagonists
  • Dopamine Uptake Inhibitors
  • Cocaine