title: Neurobiological dissociation of retrieval and reconsolidation of cocaine-associated memory.
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.
authors: Department of Psychology, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin 53201-0413, USA.
authors: James M
authors: JM
authors: Otis
authors: Kidane B
authors: KB
authors: Dashew
authors: Devin
authors: D
authors: Mueller
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000679:Amygdala / Q000187:drug effects; D000818:Animals; D001245:Association Learning / Q000187:drug effects*; D003042:Cocaine / Q000008:administration & dosage*; D003216:Conditioning, Operant / Q000187:drug effects*; D003463:Cues; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage*; D005108:Extinction, Psychological / Q000187:drug effects; D008297:Male; D008568:Memory / Q000187:drug effects*; D017397:Prefrontal Cortex / Q000187:drug effects; D051381:Rats; D020318:Rats, Long-Evans
chemical_list: D000319:Adrenergic beta-Antagonists; D018765:Dopamine Uptake Inhibitors; D003042:Cocaine