Calcium-Permeable AMPA Receptors Are Present in Nucleus Accumbens Synapses after Prolonged Withdrawal from Cocaine Self-Administration But Not Experimenter-Administered Cocaine
Calcium-Permeable AMPA Receptors Are Present in Nucleus Accumbens Synapses after Prolonged Withdrawal from Cocaine Self-Administration But Not Experimenter-Administered Cocaine
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DOI：
10.1523/jneurosci.0350-11.2011
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发表时间：
2011-04-13
影响因子：
5.3
通讯作者：
Marinelli, Michela
中科院分区：
文献类型：
--
作者：
McCutcheon, James E.;Wang, Xiaoting;Marinelli, Michela
重复非偶然的可卡因注射会导致行为致敏，以戒断依赖性方式增加啮齿动物伏隔核（NAc）中AMPA受体（AMPAR）的传递。在停药日（WD）10-21，这归因于含GluA 1A 2的AMPAR的上调。然而，在年轻小鼠中，在从重复的非偶然可卡因注射中较长时间戒断（WD 35）后，观察到缺乏GluA 2/Ca 2+可渗透的AMPAR（CP-AMPAR）的突触掺入（Mameli等人，2009年）。CP-AMPAR以前仅在延长（WD 30-WD 47）从延长的可卡因自我给药中戒断后在NAc突触中观察到。我们的目标是确定大鼠在成年期接受重复的非偶然性可卡因注射是否在长时间戒断后在NAc中同样表现出CP-AMPAR。为了进行比较，我们开始在延长使用可卡因自我给药后的WD 35-WD 49评估CP-AMPAR。与我们之前的结果一致，全细胞记录显示了向内整流的AMPAR EPSC，这是CP-AMPAR的标志。这在核和壳中都观察到。接下来，我们在每天8次非偶然可卡因注射的成年大鼠中进行了相同的分析，并在WD 35-WD 49进行了记录。核和壳的AMPAR EPSCs不显示内向整流，对CP-AMPAR的选择性拮抗剂1-naphthylacetylspermine不敏感。在这一长时间的停药期后，仍然可以证明运动致敏，尽管在早期停药时观察到的含GluA 1A 2的AMPAR的上调不再被检测到。总之，在成年大鼠中，突触CP-AMPAR在NAc中的积累发生在从长期使用可卡因自我给药中长时间戒断后，但在从非偶然可卡因注射中长时间戒断后不会发生。
Repeated noncontingent cocaine injections, which lead to behavioral sensitization, increase AMPA receptor (AMPAR) transmission in the rodent nucleus accumbens (NAc) in a withdrawal-dependent manner. On withdrawal days (WD) 10-21, this is attributable to upregulation of GluA1A2-containing AMPARs. However, synaptic incorporation of GluA2-lacking/Ca2+-permeable AMPARs (CP-AMPARs) was observed after longer withdrawal (WD35) from repeated noncontingent cocaine injections in young mice (Mameli et al., 2009). CP-AMPARs had previously been observed in NAc synapses only after prolonged (WD30-WD47) withdrawal from extended-access cocaine self-administration. Our goal was to determine whether rats receiving repeated noncontingent cocaine injections during adulthood similarly exhibit CP-AMPARs in the NAc after prolonged withdrawal. For comparison, we began by evaluating CP-AMPARs on WD35-WD49 after extended-access cocaine self-administration. Confirming our previous results, whole-cell recordings revealed inwardly rectifying AMPAR EPSCs, a hallmark of CP-AMPARs. This was observed in both core and shell. Next, we conducted the same analysis in adult rats treated with eight daily noncontingent cocaine injections and recorded on WD35-WD49. AMPAR EPSCs in core and shell did not show inward rectification and were insensitive to 1-naphthylacetylspermine (a selective antagonist of CP-AMPARs). Locomotor sensitization could still be demonstrated after this long withdrawal period, although the upregulation of GluA1A2-containing AMPARs observed at earlier withdrawal times was no longer detected. In conclusion, in adult rats, accumulation of synaptic CP-AMPARs in the NAc occurs after prolonged withdrawal from extended-access cocaine self-administration but not after prolonged withdrawal from noncontingent cocaine injections.