Bowers B J, Wehner J M
Institute for Behavioral Genetics, University of Colorado, Boulder 80309.
Brain Res Bull. 1989 Jul-Aug;23(1-2):53-9. doi: 10.1016/0361-9230(89)90163-9.
The interaction of stress and ethanol with the GABA/BZ receptor system was evaluated in LS and SS mice. The effects of two separate in vivo treatments, a 2.5 g/kg injection of ethanol or a behavioral stressor, on GABA-enhanced [3H]-FNZ binding were nearly identical in both lines of mice. A 2.5 g/kg ethanol- or stress-pretreatment resulted in increased enhancement in SS cortex, but not LS. In cerebellum, treatment effects were demonstrated in both SS and LS mice. Intraperitoneal injections of increasing doses of ethanol produced biphasic stimulation of GABA-enhanced [3H]-FNZ binding in LS brain regions, but not SS. Adrenalectomies performed one week prior to ethanol administration produced a loss of ethanol enhancement in cerebellum of both lines. However, in cortex, removal of the adrenals had no effect. The in vitro addition of 30 mM ethanol to brain preparations incubated at 37 degrees C from stressed and unstressed animals resulted in greater enhancement of binding in cortex, but not cerebellum of stressed mice. Differences in the degree of enhancement between the lines of mice were lost if the animals were stressed prior to sacrifice or if membrane preparations were incubated at 4 degrees C. The results of this study suggest that the interaction between ethanol and stress is mediated by the GABAergic system, but responses vary dependent on brain region, dose of ethanol, and degree of ethanol sensitivity.
在LS和SS小鼠中评估了应激和乙醇与GABA/BZ受体系统的相互作用。两种单独的体内处理,即注射2.5 g/kg乙醇或施加行为应激源,对GABA增强的[3H]-氟硝西泮结合的影响在两种品系小鼠中几乎相同。2.5 g/kg乙醇预处理或应激预处理导致SS小鼠皮质中的增强作用增加,但LS小鼠中没有。在小脑中,SS和LS小鼠均表现出处理效应。腹腔注射递增剂量的乙醇在LS小鼠脑区对GABA增强的[3H]-氟硝西泮结合产生双相刺激,但SS小鼠中没有。在乙醇给药前一周进行肾上腺切除术导致两个品系小鼠小脑的乙醇增强作用丧失。然而,在皮质中,切除肾上腺没有影响。在37℃下对来自应激和未应激动物的脑制备物进行体外添加30 mM乙醇,导致应激小鼠皮质中的结合增强更大,但小脑中没有。如果在处死前对动物进行应激处理,或者如果膜制备物在4℃下孵育,则小鼠品系之间增强程度的差异消失。本研究结果表明,乙醇和应激之间的相互作用由GABA能系统介导,但反应因脑区、乙醇剂量和乙醇敏感性程度而异。