Effects of Ethanol on Anxiety in Adolescent Mice

乙醇对青春期小鼠焦虑的影响

• 批准号: 6938456
• 负责人: KARA Irene GABRIEL
• 金额: $ 5万
• 依托单位: CALIFORNIA STATE UNIVERSITY HAYWARD
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-06-01 至 2009-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6938456
• 关键词: GABA receptor; age difference; animal puberty; anxiety; behavioral /social science research tag; behavioral genetics; benzodiazepines; developmental neurobiology; diazepam; drug withdrawal; ethanol; immature animal; laboratory mouse; mature animal; pharmacogenetics; pharmacokinetics; psychopharmacology; receptor expression

The goal of this proposal is to investigate developmental differences in ethanol responsiveness and in the biological substrates that underlie ethanol's effects. Specifically, the proposed experiments will examine the role of GABA-A receptor activity in ethanol-induced changes in anxiety in adolescent and adult BALB/cByJ and C57BL/6J mice. Initial experiments will characterize the anxiety-reducing (i.e., anxiolytic) effects of acute ethanol exposure (0, 1, 2 or 3 g/kg) in adolescent and aduit mice on three tests of anxiety-like behavior, the elevated zero-maze, the light/dark choice test, and novel object exploration (i.e., cork gnawing). After examining the behavioral effects of the GABA-A receptor antagonist, picrotoxin (0, 0.75, or 2.5 mg/kg), on the above tests, the ability of picrotoxin to attenuate or block ethanol's anxiolytic effects in adolescent and adult mice will be determined. A second series of experiments will characterize the anxiety-increasing (i.e., anxiogenic) effects of ethanol withdrawal (0 or 4 g/kg) in adolescent and adult BALB/cByJ and C57BL/6J mice (following determination of blood ethanol clearance rates). Because drugs that enhance GABA-A receptor activity, such as benzodiazepines, have been shown to attenuate withdrawal-induced increases in anxiety in adults, we will examine the ability of the benzodiazepine, diazepam (0, 1 or 2 mg/kg) to attenuate the anxiogenic effects of ethanol withdrawal in adolescent and adult mice. These experiments will provide data on anxiety-like behavior and ethanol responsiveness in adolescent animals as well as determine if behavioral differences in adolescent animals are mediated by developmental alterations in GABA-A receptor activity. Comparisons of inbred strains will permit a preliminary examination into the manner in which genetic influences on ethanol responses vary over ontogeny. It is hoped that a better understanding of ethanol's effects in adolescence will aid in the development of more effective prevention strategies or treatment for human adolescents.

该提案的目的是研究乙醇反应性的发育差异以及乙醇作用构成的生物底物。具体而言，提出的实验将检查GABA-A受体活性在乙醇诱导的青少年和成人BALB/CBYJ和C57BL/6J小鼠中焦虑变化中的作用。最初的实验将表征急性乙醇暴露（0、1、2或3 g/kg）在青少年和ADUIT小鼠中的焦虑减轻（即抗焦虑性）的影响，对焦虑般的行为，较高的零迷宫，轻度/暗选择测试以及新颖的对象探索（即，较新的对象）的三种测试（即焦虑症）。在检查了GABA-A受体拮抗剂的行为效应之后（0，0.75或 2.5 mg/kg），在上述测试中，将确定野毒素减弱或阻断乙醇在青少年和成年小鼠中的抗焦虑作用的能力。第二系列实验将表征乙醇戒断（0或4 g/kg）在青少年和成人BALB/CBYJ和C57BL/6J小鼠中的焦虑症（即焦虑生成）作用（遵循血液乙醇清除率的确定）。由于增强GABA-A受体活性的药物（例如苯二氮卓类药物）已被证明可减弱成人戒断引起的焦虑症的增加，因此我们将检查苯并二氮卓类地西ep（0、1或2 mg/kg）的能力 减轻乙醇在青少年和成年小鼠中的焦虑作用。这些实验将提供有关青少年动物中焦虑样行为和乙醇反应性的数据，并确定青少年动物的行为差异是否是通过GABA-A受体活性的发育改变来介导的。近交菌株的比较将允许对遗传影响乙醇反应的方式进行初步检查。希望更好地了解乙醇在青春期的影响将有助于制定更有效的预防策略或为人类青少年的治疗。