Nucleus accumbens dopamine D1 receptors regulate the expression of ethanol-induced behavioural sensitization
Nucleus accumbens dopamine D1 receptors regulate the expression of ethanol-induced behavioural sensitization
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DOI：
10.1017/s1461145710000441
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发表时间：
2011-03-01
影响因子：
4.8
通讯作者：
Oliveira Souza-Formigoni, Maria Lucia
中科院分区：
文献类型：
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作者：
Abrahao, Karina Possa;Quadros, Isabel Marian Hartmann;Oliveira Souza-Formigoni, Maria Lucia
重复使用乙醇可诱导行为致敏，定义为运动刺激物作用的进行性增强。这一过程与中边缘通路和伏隔核的神经适应有关。本研究的目的是分析多巴胺D-1受体（D1R）参与对不同水平乙醇致敏的小鼠对D1R的激动剂和拮抗剂的运动反应。在三个单独的实验中，小鼠每隔一天给予2.2 g/kg乙醇或生理盐水，连续10 d。根据最后一天的运动反应，将乙醇处理的动物分为致敏组和非致敏组。治疗后，小鼠分别注射4或8 mg/kg SKF-38393 (ip)，一种D1R激动剂（expt 1）；或加入0.01或0.1 mg/kg SCH-23390（一种D1R拮抗剂），然后再加入2.2 g/kg乙醇（一种ip）（实验2）。在实验3中，小鼠分别注射伏隔核内（nac） SKF-38393 （1 μ g/侧，0.2 μ l）和nac内SCH-23390 (3 μ g/侧，0.2 μ l)，然后注射2.2 g/kg乙醇（i.p）。虽然腹腔注射SKF-38393不影响小鼠的运动，但NAc内注射SKF-38393可显著增加致敏小鼠的运动活性，提示致敏小鼠在NAc中存在功能性高反应的D(1)Rs。腹腔注射和NAc内注射SCH-23390均可阻断乙醇致敏表达，提示NAc D(1)Rs的激活对乙醇致敏表达至关重要。
Repeated ethanol administration may induce behavioural sensitization, defined as a progressive potentiation of locomotor stimulant effects. This process is associated with neuroadaptations in the mesolimbic pathway and the nucleus accumbens. The aim of the present study was to analyse dopamine D-1 receptor (D1R) participation in locomotor response to an agonist and an antagonist of the D1R in mice with different levels of sensitization to ethanol. In three separate experiments, mice received administrations of 2.2 g/kg ethanol or saline every other day for 10 d. According to their locomotor response on the last day, ethanol-treated animals were classified into two groups : sensitized or non-sensitized. After the treatment, mice were challenged with 4 or 8 mg/kg SKF-38393 (i.p.), a D1R agonist (expt 1); or with 0.01 or 0.1 mg/kg SCH-23390 (i.p.), a D1R antagonist, followed by 2.2 g/kg ethanol (i.p.) administration (expt 2). In expt 3, mice were challenged with intra-accumbens (intra-NAc) SKF-38393 (1 mu g/side, in 0.2 mu l), and with intra-NAc SCH-23390 (3 mu g/side, in 0.2 mu l) followed by 2.2 g/kg ethanol (i.p.). Although the i.p. administration of SKF-38393 did not affect the locomotion of mice, the intra-NAc administration of SKF-38393 significantly increased the locomotor activity in sensitized mice, suggesting that sensitized mice present functionally hyperresponsive D(1)Rs in the NAc. Both i.p. and intra-NAc administration of SCH-23390 blocked the expression of ethanol sensitization, suggesting that the activation of NAc D(1)Rs seems to be essential for the expression of ethanol sensitization.