Induction of multiple reinstatements of ethanol- and sucrose-seeking behavior in Long-Evans rats by the ýý-2 adrenoreceptor antagonist yohimbine.
Induction of multiple reinstatements of ethanol- and sucrose-seeking behavior in Long-Evans rats by the ýý-2 adrenoreceptor antagonist yohimbine.
复制标题
通过 α-2 肾上腺素受体拮抗剂育亨宾诱导 Long-Evans 大鼠多次恢复乙醇和蔗糖寻求行为。
DOI：
10.1007/s00213-011-2451-9
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发表时间：
2011
影响因子：
3.4
通讯作者：
Bartlett,SelenaE
中科院分区：
文献类型：
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作者：
Simms,JeffreyA;Richards,JemmaK;Mill,Douglas;Kanholm,Isabel;Holgate,JoanY;Bartlett,SelenaE
开发模型来有效地探索应激介导药物寻求行为恢复的机制，对于开发酒精使用障碍的新药物疗法至关重要。ObjectivesWe研究了使用药理应激源育亨宾的多次恢复治疗的效果，在乙醇和蔗糖寻求大鼠，以开发一个更有效的模型，应激诱导的恢复。训练Evans大鼠自我给予10%乙醇（含蔗糖褪色程序）、20%乙醇（不含蔗糖褪色程序）或5%蔗糖（30分钟操作性自我给药期），然后进行消退训练。达到灭绝标准后，在恢复期或采血前30分钟，每周分别用育亨宾溶剂和育亨宾（2 mg/kg）对动物进行一次试验。恢复和血浆皮质酮（CORT）的水平，每周确定连续4 weeks.ResultsYohimbine诱导恢复乙醇和蔗糖寻求在每4周。有趣的是，在第一次恢复期后，10%乙醇组的恢复幅度降低，但在没有蔗糖的情况下训练的20%乙醇组保持稳定。响应于注射的车辆和育亨宾的血浆CORT水平显着较高的乙醇训练的动物相比，蔗糖controls.ConclusionsThe稳定的恢复在20%乙醇组支持使用这种训练过程中的研究中使用的受试者内设计与多育亨宾恢复测试会话。此外，这些结果表明，自我服用相对适量的乙醇后，对压力源的激素反应可以改变。
RationaleDeveloping models to efficiently explore the mechanisms by which stress can mediate reinstatement of drug-seeking behavior is crucial to the development of new pharmacotherapies for alcohol use disorders.ObjectivesWe examined the effects of multiple reinstatement sessions using the pharmacological stressor, yohimbine, in ethanol- and sucrose-seeking rats in order to develop a more efficient model of stress-induced reinstatement.MethodsLong–Evans rats were trained to self-administer 10% ethanol with a sucrose-fading procedure, 20% ethanol without a sucrose-fading procedure, or 5% sucrose in 30-min operant self-administration sessions, followed by extinction training. After reaching extinction criteria, the animals were tested once per week with yohimbine vehicle and yohimbine (2 mg/kg), respectively, 30 min prior to the reinstatement sessions or blood collection. Levels of reinstatement and plasma corticosterone (CORT) were determined each week for four consecutive weeks.ResultsYohimbine induced reinstatement of ethanol- and sucrose-seeking in each of the 4 weeks. Interestingly, the magnitude of the reinstatement decreased for the 10% ethanol group after the first reinstatement session but remained stable for the 20% ethanol group trained without sucrose. Plasma CORT levels in response to injection of both vehicle and yohimbine were significantly higher in the ethanol-trained animals compared to sucrose controls.ConclusionsThe stable reinstatement in the 20% ethanol group supports the use of this training procedure in studies using within-subject designs with multiple yohimbine reinstatement test sessions. Additionally, these results indicate that the hormonal response to stressors can be altered following extinction from self-administration of relatively modest amounts of ethanol.