The NMDA antagonist MK-801 disrupts reconsolidation of a cocaine-associated memory for conditioned place preference but not for self-administration in rats
The NMDA antagonist MK-801 disrupts reconsolidation of a cocaine-associated memory for conditioned place preference but not for self-administration in rats
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DOI：
10.1101/lm.1152808
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发表时间：
2008-12-01
影响因子：
2
通讯作者：
Sorg, Barbara A.
中科院分区：
文献类型：
--
作者：
Brown, Travis E.;Lee, Brian R.;Sorg, Barbara A.
最近的研究表明，与药物有关的记忆在暴露于环境线索后重新激活，并可能经历重新巩固，这一过程可以加强记忆。相反，再巩固可能会被某些药物破坏，从而削弱与药物相关的记忆。一些研究已经证明了药物诱导的条件性位置偏爱(CPP)任务破坏了记忆的重新巩固，但还没有研究探索在注射可卡因后，与可卡因相关的记忆是否也会同样地被破坏，可卡因引发的注射有力地恢复了寻找毒品的行为。在这里，我们使用可卡因诱导的CPP和可卡因自身给药来研究N-甲基-D-天冬氨酸受体拮抗剂(+)-5甲基-10，11-二氢-5H-二苯并[a，d]环庚烯-5，10-亚胺马来酸(MK-801)是否会抑制随后的可卡因诱导的恢复(再巩固中断)。在CPP环境中可卡因相关记忆重新激活之前，系统注射MK-801(0.05或0.20 mg/kg)可减弱随后可卡因诱导的恢复，而未在CPP环境中重新激活的大鼠则没有中断。然而，在接受自我管理可卡因训练的大鼠中，在两种不同类型的重新激活过程中的任何一种之前，系统地给药MK-801对随后可卡因启动的杠杆按压行为的恢复没有影响。因此，全身给药MK-801破坏了CPP的可卡因相关记忆的重新巩固，但对自我给药没有影响。这些发现表明，可卡因-CPP和自我给药没有使用类似的神经化学过程来破坏再巩固，或者自我给药大鼠的可卡因相关记忆没有经历重新巩固，这是通过可卡因恢复条件下的杠杆按压行为来评估的。
Recent research suggests that drug-related memories are reactivated after exposure to environmental cues and may undergo reconsolidation, a process that can strengthen memories. Conversely, reconsolidation may be disrupted by certain pharmacological agents such that the drug-associated memory is weakened. Several studies have demonstrated disruption of memory reconsolidation using a drug-induced conditioned place preference (CPP) task, but no studies have explored whether cocaine-associated memories can be similarly disrupted in cocaine self-administering animals after a cocaine priming injection, which powerfully reinstates drug-seeking behavior. Here we used cocaine-induced CPP and cocaine self-administration to investigate whether the N-methyl-D-aspartate receptor antagonist (+)-5methyl- 10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK-801) given just prior to reactivation sessions would suppress subsequent cocaine-primed reinstatement (disruption of reconsolidation). Systemic injection of MK-801 (0.05 or 0.20 mg/kg administered intraperitoneally) in rats just prior to reactivation of the cocaine-associated memory in the CPP context attenuated subsequent cocaine-primed reinstatement, while no disruption occurred in rats that did not receive reactivation in the CPP context. However, in rats trained to self-administer cocaine, systemic administration of MK-801 just prior to either of two different types of reactivation sessions had no effect on subsequent cocaine-primed reinstatement of lever-pressing behavior. Thus, systemic administration of MK-801 disrupted the reconsolidation of a cocaine-associated memory for CPP but not for self-administration. These findings suggest that cocaine-CPP and self-administration do not use similar neurochemical processes to disrupt reconsolidation or that cocaine-associated memories in self-administering rats do not undergo reconsolidation, as assessed by lever-pressing behavior under cocaine reinstatement conditions.