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首页> 外文期刊>The European Journal of Neuroscience >Role of GluR1 expression in nucleus accumbens neurons in cocaine sensitization and cocaine-seeking behavior.
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Role of GluR1 expression in nucleus accumbens neurons in cocaine sensitization and cocaine-seeking behavior.

机译：伏伏核神经元中的GluR1表达在可卡因敏化和可卡因寻找行为中的作用。

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Chronic cocaine use reduces glutamate levels in the nucleus accumbens (NAc), and is associated with experience-dependent changes in (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) glutamate receptor membrane expression in NAc neurons. These changes accompany behavioral sensitization to cocaine and increased susceptibility to cocaine relapse. The functional relationship between neuroplasticity in AMPA receptors and the behavioral manifestation of cocaine addiction remains unclear. Thus, we examined the behavioral effects of up- and downregulating basal AMPA receptor function in the NAc core and shell using viral-mediated gene transfer of wild-type glutamate receptor 1 (wt-GluR1) or a dominant-negative pore-dead GluR1 (pd-GluR1), respectively. Transient increases in wt-GluR1 during or after cocaine treatments diminished the development of cocaine sensitization, while pd-GluR1 expression exacerbated cocaine sensitization. Parallel changes were found in D2, but not D1, receptor-mediated behavioral responses. As a correlate of the sensitization experiments, we overexpressed wt- or pd-GluR1 in the NAc core during cocaine self-administration, and tested the effects on subsequent drug-seeking behavior 3 weeks after overexpression declined. wt-GluR1 overexpression during self-administration had no effect on cocaine intake, but subsequently reduced cocaine seeking in extinction and cocaine-induced reinstatement, whereas pd-GluR1 facilitated cocaine-induced reinstatement. When overexpressed during reinstatement tests, wt-GluR1 directly attenuated cocaine- and D2 agonist-induced reinstatement, while pd-GluR1 enhanced reinstatement. In both experimental procedures, neither wt- nor pd-GluR1 expression affected cue-induced reinstatement. Together, these results suggest that degrading basal AMPA receptor function in NAc neurons is sufficient to facilitate relapse via sensitization in D2 receptor responses, whereas elevating basal AMPA receptor function attenuates these behaviors.
机译：长期使用可卡因可降低伏伏核（NAc）中的谷氨酸水平，并与（+/-）-α-氨基-3-羟基-5-甲基异恶唑-4-丙酸（AMPA）谷氨酸受体的经验依赖性变化有关NAc神经元中的膜表达。这些变化伴随着对可卡因的行为敏感性以及对可卡因复发的易感性增加。 AMPA受体的神经可塑性与可卡因成瘾的行为表现之间的功能关系尚不清楚。因此，我们使用病毒介导的野生型谷氨酸受体1（wt-GluR1）或显性阴性毛孔死GluR1（wt-GluR1）介导的基因转移，研究了上调和下调基础AMPA受体在NAc核和壳中的行为效应。 pd-GluR1）。在可卡因治疗期间或之后，wt-GluR1的瞬时增加减少了可卡因致敏作用的发展，而pd-GluR1的表达加剧了可卡因致敏作用。在D2受体介导的行为反应中发现了平行变化，但在D1中没有发现。作为致敏实验的一个相关因素，我们在可卡因自我给药过程中在NAc核心中过表达wt-或pd-GluR1，并在过表达下降3周后测试了其对随后用药行为的影响。自我管理期间wt-GluR1的过表达对可卡因的摄入没有影响，但随后在灭绝和可卡因诱导的恢复中减少了可卡因的寻找，而pd-GluR1促进了可卡因诱导的恢复。当在恢复测试中过度表达时，wt-GluR1直接减弱可卡因和D2激动剂诱导的恢复，而pd-GluR1增强恢复。在这两个实验程序中，wt-和pd-GluR1的表达均不影响提示诱导的恢复。总之，这些结果表明，NAc神经元中基础AMPA受体功能的降低足以通过D2受体应答中的致敏促进复发，而基础AMPA受体功能的升高则减弱了这些行为。

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