Department of Psychiatry, SUNY Upstate Medical University at Syracuse, Syracuse, NY 13210, USA.
Pharmacol Biochem Behav. 2020 May;192:172911. doi: 10.1016/j.pbb.2020.172911. Epub 2020 Mar 19.
An extensive literature has validated the critical importance of a brief post-trial consolidation period for the incorporation of an experience into memory. Importantly, during this active consolidation state the memory formation is vulnerable to modification. While the subsequent stabilization of the memory makes it relatively resistant to modification, conditioned drug cues that re-activate the cue drug state association can initiate a re-consolidation process and during this re-consolidation the drug-cue association again becomes briefly unstable and sensitive to modification by post-trial treatments. Although most post-trial treatments shown to interact with memory consolidation processes have been used with instrumental learning protocols, this review is focused on recent findings that indicate that psycho-stimulant drug responses induced by apomorphine and morphine during the post-trial consolidation/re-consolidation state can become incorporated into the memory process. As a consequence, these post-trial drug treatment effects can be expressed in a subsequent non-drug test as behavioral responses comparable to the drug induced responses. In fact, apomorphine and morphine when administered post-trial can induce sensitization/conditioned effects that mirror the effects generated when these same drugs are administered in the presence of contextual cues. In addition, it has been shown that apomorphine given at stimulant/inhibitory dopaminergic dose levels post-trial during re-consolidation of a conditioned drug behavior can intensify/reverse the drug conditioning previously induced by apomorphine, morphine or haloperidol. The apparent efficacy of a post-trial drug state induced by a psycho-stimulant drug during consolidation/re-consolidation to become incorporated into contextual memory points up an alternative way, in addition to Pavlovian conditioning, by which psycho-stimulant drug effects can become embedded into an engram activated by contextual cues. These findings further suggest that drug treatments can be used to counter-condition the re-consolidated conditioned addictive drug response to substantially reduce the salience and motivational significance the conditioned association induced by the addictive drug.
大量文献证实，短暂的试验后巩固期对于将经验纳入记忆具有至关重要的作用。重要的是，在这个主动巩固状态下，记忆形成容易受到影响。虽然随后记忆的稳定使其相对不易受到影响，但重新激活线索药物状态关联的条件性药物线索可以启动再巩固过程，在此再巩固过程中，药物线索关联再次变得短暂不稳定，并容易受到试验后治疗的影响。尽管大多数已显示与记忆巩固过程相互作用的试验后治疗方法已用于工具性学习方案，但本综述重点介绍了最近的发现，表明阿扑吗啡和吗啡在试验后巩固/再巩固状态下诱导的精神兴奋剂药物反应可以被纳入记忆过程。因此，这些试验后药物治疗效果可以在随后的非药物测试中表现为与药物诱导反应相当的行为反应。事实上，阿扑吗啡和吗啡在试验后给药时可以诱导类似的敏化/条件作用，这些作用与这些相同的药物在环境线索存在下给药时产生的作用相似。此外，已经表明，在条件性药物行为的再巩固期间，在刺激/抑制多巴胺能剂量水平下给予阿扑吗啡后可以增强/逆转先前由阿扑吗啡、吗啡或氟哌啶醇诱导的药物条件作用。在巩固/再巩固期间，精神兴奋剂药物状态诱导的试验后药物状态被纳入上下文记忆的明显效果，除了巴甫洛夫条件作用之外，提供了另一种方式，使精神兴奋剂药物的作用可以嵌入由环境线索激活的记忆痕迹中。这些发现进一步表明，药物治疗可以用于条件反射性地治疗再巩固的条件性成瘾药物反应，从而大大降低成瘾药物诱导的条件关联的显著性和动机意义。
