Assessing appetitive and consummatory phases of ethanol self-administration in C57BL/6J mice under operant conditions: regulation by mGlu5 receptor antagonism
Assessing appetitive and consummatory phases of ethanol self-administration in C57BL/6J mice under operant conditions: regulation by mGlu5 receptor antagonism
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DOI：
10.1007/s00213-006-0583-0
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发表时间：
2007-01-01
影响因子：
3.4
通讯作者：
Lawrence, Andrew J.
中科院分区：
文献类型：
--
作者：
Cowen, Michael S.;Krstew, Elena;Lawrence, Andrew J.
小鼠酒精消费和酒精寻找行为模型的建立对于了解药物滥用的潜在机制特别重要，因为这些模型可以分析特定的基因对药物寻求行为的影响，以及潜在的治疗方法与基因的相互作用。然而，目前的模型有一些局限性，特别是不能分别检查食欲和食欲行为。材料和方法在本研究中，C57BL/6小鼠被训练为在修改的操作规程中自我给予10%的乙醇，以允许清晰地划分食欲和食欲阶段。代谢性谷氨酸5(MGlu5)受体拮抗剂3-[(2-methyl-1，3-thiazol-4-yl)ethynyl]-pyridine(MTEP)的使用证实了这一过程的有效性。结果在明暗周期的黑暗阶段，间歇性获取(每隔2天或3天)的有限获取消耗导致小鼠高水平的获取。MTEP使乙醇消耗量和对乙醇的食欲反应均呈剂量依赖性减少。结论该模型为研究小鼠酒精摄取的食欲阶段和消耗阶段提供了一个有用的范式；此外，数据表明mGlu5受体参与了这两个阶段的研究。
Rationale The development of mouse models of ethanol consumption and ethanol-seeking behavior is of particular importance in understanding the underlying mechanisms of drug abuse because these models can enable an analysis of an effect of specific genotype on drug-seeking behavior and the interaction of potential therapeutics with genotype. However, there are some limitations with present models, notably the inability to examine appetitive and consummatory behavior separately.Materials and methods In the present study, C57BL/6 mice were trained to self-administer 10% ethanol in a modified operant protocol that allowed a clear delineation of consummatory and appetitive phases. The utility of this procedure was confirmed with the use of the metabotropic glutamate 5 (mGlu5) receptor antagonist 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]-pyridine (MTEP).Results Limited-access consumption during the dark phase of the light-dark cycle with intermittent access (every second or third day) led to a high level of consumption by the mice. MTEP caused a dose-dependent decrease in both the consumption of ethanol and the appetitive response for ethanol. Furthermore, this effect was unrelated to any effect of MTEP on locomotor activity.Conclusions The model provides a useful paradigm for examining both the appetitive and consummatory phases of ethanol consumption in mice; furthermore, the data indicate mGlu5 receptors are involved in both phases.