Rustay N R, Boehm S L, Schafer G L, Browman K E, Erwin V G, Crabbe J C
Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR 97201, USA.
Pharmacol Biochem Behav. 2001 Sep;70(1):167-74. doi: 10.1016/s0091-3057(01)00595-0.
Acute functional tolerance (AFT) manifests as rapid adaptation during a single ethanol exposure, leading to a decrease in the behavioral response to ethanol. In order to investigate the genetic and environmental components of the development of AFT, mice were selectively bred in replicate from HS/Ibg mice. High (HAFT) and low (LAFT) acute functional tolerance selected lines were bred to differ in the rate of development and magnitude of AFT to ethanol's intoxicating effects using a static dowel-balancing task. In the present set of experiments, HAFT and LAFT mice were tested for development of AFT on a fixed-speed rotarod using a protocol similar to that for which they were selected. HAFT mice developed greater AFT to ethanol than did LAFT mice. In a separate experiment, other mice from these lines were tested for initial sensitivity and the development of chronic tolerance to ethanol-induced hypothermia, and ethanol-induced incoordination in the grid test. Previous research has detected possible common genetic control of these phenotypes. No differences between lines were found in initial sensitivity to ethanol or in the development or magnitude of chronic tolerance in either test. These experiments show that genetic factors influencing the development of acute tolerance to ethanol-induced intoxication are at least partially distinct from those influencing initial sensitivity and the development of chronic tolerance to ethanol-induced hypothermia and incoordination. Furthermore, these experiments show that AFT measured by the stationary dowel generalizes to AFT measured by the fixed-speed rotarod.
急性功能性耐受（AFT）表现为单次乙醇暴露期间的快速适应，导致对乙醇行为反应的降低。为了研究AFT发展的遗传和环境成分，从HS/Ibg小鼠中重复选择性培育小鼠。利用静态销钉平衡任务，培育出高（HAFT）和低（LAFT）急性功能性耐受选择品系，使其在对乙醇中毒效应的AFT发展速率和程度上存在差异。在本系列实验中，使用与选择它们时相似的方案，在固定速度的转棒上对HAFT和LAFT小鼠进行AFT发展测试。HAFT小鼠比LAFT小鼠对乙醇产生了更大的AFT。在另一项实验中，对这些品系的其他小鼠进行了初始敏感性测试，以及对乙醇诱导的体温过低和网格试验中乙醇诱导的不协调的慢性耐受发展测试。先前的研究已经检测到这些表型可能存在共同的遗传控制。在乙醇初始敏感性或两项测试中慢性耐受的发展或程度方面，品系之间未发现差异。这些实验表明，影响对乙醇诱导中毒的急性耐受发展的遗传因素至少部分不同于影响初始敏感性以及对乙醇诱导的体温过低和不协调的慢性耐受发展的遗传因素。此外，这些实验表明，通过固定销钉测量的AFT可推广到通过固定速度转棒测量的AFT。
