Long-term changes in connexin32 gap junction protein and mRNA expression following cocaine self-administration in rats
Long-term changes in connexin32 gap junction protein and mRNA expression following cocaine self-administration in rats
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DOI：
10.1046/j.1460-9568.1999.00752.x
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发表时间：
1999-09-01
影响因子：
3.4
通讯作者：
Roberts, DCS
中科院分区：
文献类型：
--
作者：
Bennett, SAL;Arnold, JM;Roberts, DCS
相当多的证据表明，多巴胺在可卡因的强化作用中起着关键作用。由于多巴胺已被证明是眼睛和大脑中间隙连接通讯的关键调节剂，我们试图研究延长静脉内可卡因自我管理是否会影响间隙连接通道形成蛋白（连接蛋白）的表达。使用ELISA，Western分析，免疫组化，半定量逆转录聚合酶链反应（RT-PCR），和非放射性原位杂交，我们表明，退出慢性可卡因自我管理的原因，在连接蛋白32（Cx 32）的表达在最后一次可卡因注射后2，7和21天的持续变化，在脑桥核和海马。Cx 32蛋白和mRNA水平的持续下降，在已涉及可卡因的渴望（即，海马结构的脑髓核和子域）的区域。在慢性可卡因暴露后变得过度兴奋的区域（即CA 1海马神经元）中注意到间隙连接蛋白和mRNA表达的进行性增加。我们推测，间隙连接通讯可能是至关重要的参与强化过程和滥用药物产生的神经适应性变化。
Considerable evidence indicates a critical role for dopamine in the reinforcing effects of cocaine. Because dopamine has been shown to be a critical modulator of gap junction communication in both eye and brain, we sought to examine whether extended intravenous cocaine self-administration would affect the expression of gap junction channel-forming proteins (connexins). Using ELISA, Western analysis, immunohistochemistry, semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR), and non-radioactive in situ hybridization, we demonstrate that withdrawal from chronic cocaine self-administration causes lasting changes in connexin32 (Cx32) expression in the nucleus accumbens and hippocampus at 2, 7 and 21 days after the last cocaine injection. A sustained decrease in Cx32 protein and mRNA levels is noted in areas that have been implicated in cocaine craving (i.e. nucleus accumbens and subfields of the hippocampal formation). A progressive increase in gap junction protein and mRNA expression is noted in areas that become hyperexcitable after chronic cocaine exposure (i.e. CA1 hippocampal neurons). We speculate that gap junction communication may be critically involved in reinforcement processes and neuroadaptive changes produced by drugs of abuse.