Analysis of the Reconsolidation Phenomenon in a Morphine Conditioned Place Preference.

摘要

Memories once acquired, are retained in a stable state that is relatively impervious to change. However, following reactivation these memories are destabilized and require a reconsolidation process to once again be stabilized. If the reconsolidation process is disrupted, amnesia will ensue. This has opened the possibility that reconsolidation could be used a therapeutic tool for attenuating detrimental memories such as those that govern post-traumatic stress disorder and drug addiction. Contextual cues previously associated with rewarding drugs induce powerful cravings which are believed to be a major cause of relapse. Disrupting memory reconsolidation for these associations may provide a means to attenuate cue-induced craving and relapse. This thesis shows that post-reactivation administration of the amnestic agents propranolol and midazolam will disrupt a morphine place preference in a manner consistent with reconsolidation blockade. A further study shows that over-learning acts as a boundary condition that inhibits reconsolidation. However the impact of memory strength can be overcome by allowing the memory to age and decay prior to reactivation. Another study demonstrates that post-reactivation propranolol treatment disrupts reconsolidation when administered immediately after a first, but not a second, non-reinforced reactivation session. This suggests that a certain degree of novelty is required at the time of reactivation for reconsolidation to be triggered. Finally the impact of drug dependence on the reconsolidation phenomenon is explored and shown to produce resistance to post-reactivation amnesia. In fact, it reverses the effect of propranolol and results in an enhancement of the preference for the drug-paired cues. These findings support the concept of reconsolidation as a therapeutic approach for treating cue-induced relapse in former drug addicts, but highlight the critical impact that prior dependence may have on the phenomenon.