科研之友
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摘要
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 beta-adrenergic receptor (beta-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 beta-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, beta-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 beta-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 beta-AR antagonist prevents norepinephrine-induced potentiation of PL-mPFC pyramidal cell and beta-aminobutyric-acid (GABA) interneuron excitability. Thus, targeted beta-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.
- 出版日期2013-1-16
