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首页> 外文期刊>Addiction biology >Chronic cocaine self-administration modulates ERK1/2 and CREB responses to dopamine receptor agonists in striatal slices
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Chronic cocaine self-administration modulates ERK1/2 and CREB responses to dopamine receptor agonists in striatal slices

机译：慢性可卡因自我管理可调节纹状体切片中ERK1 / 2和CREB对多巴胺受体激动剂的反应

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Cocaine abuse leads to adaptations in brain reward circuits, where dopaminergic neurotransmission is a fundamental component. We hypothesized that chronic cocaine self-administration could influence dopamine D1 and D2 receptor activation of extracellular signal-regulated protein kinase 1 and 2 (ERK1/2) and cyclic adenosine monophosphate response element-binding protein (CREB) phosphorylation. Male Sprague Dawley rats were exposed to cocaine self-administration for 6-11 weeks. Brains from sham controls and cocaine rats were extracted 1 day after the last session, and slices obtained from the striatum and nucleus accumbens (NAc) were incubated in vitro with or without the D1R agonist SKF38393 or the D2R agonist quinpirole. We found that cocaine self-administration led to a reduction in the capacity of D1R to activate ERK1/2 phosphorylation as compared with control rats. Cocaine self-administration also reduced D1R agonist-induced CREB phosphorylation in striatal slices, suggesting a downregulation of D1R signaling. D2R-induced ERK1/2 phosphorylation appeared blunted in striatal slices from cocaine rats. In contrast, surprisingly, cocaine self-administration strongly potentiated D2R agonist-induced CREB phosphorylation selectively in the NAc portion of the slices. Altered agonist-induced signaling was independent of total ERK1/2 and CREB expression. Our finding that selected cellular D2R responses to CREB were strengthened by cocaine self-administration could be relevant to understand how dopaminergic receptors participate in cocaine-induced behaviors.
机译：可卡因的滥用导致大脑奖励回路的适应，而多巴胺能神经传递是其中的基本组成部分。我们假设慢性可卡因的自我管理可能会影响细胞外信号调节蛋白激酶1和2（ERK1 / 2）和环状单磷酸腺苷反应元件结合蛋白（CREB）磷酸化的多巴胺D1和D2受体激活。将雄性Sprague Dawley大鼠暴露于可卡因自我给药6-11周。在最后一次会议后第1天，从假对照组和可卡因大鼠中提取大脑，并在有或没有D1R激动剂SKF38393或D2R激动剂喹吡罗的情况下体外培养从纹状体和伏隔核（NAc）获得的切片。我们发现，与对照大鼠相比，可卡因的自我给药导致D1R激活ERK1 / 2磷酸化的能力降低。可卡因的自我给药还可以减少纹状体切片中D1R激动剂诱导的CREB磷酸化，表明D1R信号的下调。可卡因大鼠的纹状体切片中D2R诱导的ERK1 / 2磷酸化作用减弱。相反，令人惊讶地，可卡因的自我给药在切片的NAc部分中选择性地强烈增强了D2R激动剂诱导的CREB磷酸化。激动剂诱导的信号改变与总ERK1 / 2和CREB表达无关。我们的发现，可卡因自我给药可增强对CREB的选择性细胞D2R反应，这可能与了解多巴胺能受体如何参与可卡因诱导的行为有关。

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