Neurobiological dissociation of retrieval and reconsolidation of cocaine-associated memory.
Neurobiological dissociation of retrieval and reconsolidation of cocaine-associated memory.
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DOI：
10.1523/jneurosci.3463-12.2013
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发表时间：
2013-01-16
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影响因子：
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通讯作者：
Mueller D
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文献类型：
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作者：
Otis JM;Dashew KB;Mueller D
即使在长期戒断之后，与毒品有关的线索也会引起吸毒。因此，这些习得性联系的中断将限制复发的易感性。药物相关的记忆在提取过程中和之后不久的记忆重新巩固过程中容易受到长期破坏。最近的证据表明，修复和再巩固依赖于β-肾上腺素能受体（β-AR）的激活。尽管如此，提取和再巩固是否依赖于相同或不同的神经机制是未知的。前边缘内侧前额叶皮层（PL-mPFC）和基底外侧杏仁核（BLA）参与了联想记忆的表达和再巩固。因此，我们研究了可卡因相关的记忆提取和再巩固在大鼠PL mPFC和BLA内的β-AR激活的必要性。在可卡因诱导的条件性位置偏爱（CPP）恢复试验之前或之后立即，将β-AR拮抗剂注入PL-mPFC或BLA，然后进行每日测试。在CPP试验之前（而不是之后）注入PL-mPFC会破坏CPP记忆提取，并在随后的试验中诱导持续的提取缺陷。相反，BLA β-AR阻断对初始CPP记忆提取没有影响，但在随后的试验中阻止了CPP表达，表明再巩固中断。我们的研究结果揭示了可卡因相关的记忆提取和再巩固所需的神经机制之间的明显分离。使用膜片钳电生理学，我们还表明，β-AR拮抗剂的应用防止NE诱导的PL-mPFC锥体和GABA能神经元兴奋性的增强。因此，靶向β-AR阻断可通过降低神经元兴奋性诱导药物相关记忆恢复的长期缺陷，提供了预防线索诱导的药物寻找和复发的新方法。
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 NE-induced potentiation of PL-mPFC pyramidal and GABAergic neuronal 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.