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Inhibition of hippocampal ?-adrenergic receptors impairs retrieval but not reconsolidation of cocaine-associated memory and prevents subsequent reinstatement.

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

SUBMITTER: Otis JM

PROVIDER: S-EPMC3870790 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Norepinephrine regulates cocaine-primed reinstatement via ?1-adrenergic receptors in the medial prefrontal cortex.

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