Inhibition of Hippocampal β-adrenergic Receptors Impairs Retrieval but Not Reconsolidation of Cocaine-Associated Memory and Prevents Subsequent Reinstatement

Neuropsychopharmacology. 2014 Jan;39(2):303-10. doi: 10.1038/npp.2013.187. Epub 2013 Aug 2.


Retrieval of drug-associated memories is critical for maintaining addictive behaviors, as presentation of drug-associated cues can elicit drug seeking and relapse. Recently, we and others have demonstrated that β-adrenergic receptor (β-AR) activation is necessary for retrieval using both rat and human memory models. Importantly, blocking retrieval with β-AR antagonists persistently impairs retrieval and provides protection against subsequent reinstatement. However, the neural locus at which β-ARs are required for maintaining retrieval and subsequent reinstatement is unclear. Here, we investigated the necessity of dorsal hippocampus (dHipp) β-ARs for drug-associated memory retrieval. Using a cocaine conditioned place preference (CPP) model, we demonstrate that local dHipp β-AR blockade before a CPP test prevents CPP expression shortly and long after treatment, indicating that dHipp β-AR blockade induces a memory retrieval disruption. Furthermore, this retrieval disruption provides long-lasting protection against cocaine-induced reinstatement. The effects of β-AR blockade were dependent on memory reactivation and were not attributable to reconsolidation disruption as blockade of β-ARs immediately after a CPP test had little effect on subsequent CPP expression. Thus, cocaine-associated memory retrieval is mediated by β-AR activity within the dHipp, and disruption of this activity could prevent cue-induced drug seeking and relapse long after treatment.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Antagonists / pharmacology*
  • Animals
  • Association Learning / drug effects*
  • Association Learning / physiology
  • Cocaine / pharmacology*
  • Hippocampus / drug effects*
  • Hippocampus / physiology
  • Male
  • Memory / drug effects*
  • Memory / physiology
  • Rats
  • Rats, Long-Evans
  • Receptors, Adrenergic, beta / metabolism*


  • Adrenergic beta-Antagonists
  • Receptors, Adrenergic, beta
  • Cocaine