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

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