Koenig Heather N, Olive M Foster
Ernest Gallo Clinic & Research Center, Department of Neurology, University of California at San Francisco, 5858 Horton Street, Suite 200, Emeryville, CA 94608, USA.
Psychoneuroendocrinology. 2004 Sep;29(8):999-1003. doi: 10.1016/j.psyneuen.2003.09.004.
There is a substantial amount of evidence indicating control over ethanol intake by steroid hormones, particularly adrenal glucocorticoids. Thus far, however, studies employing pharmacological methods have failed to find effects of glucocorticoid receptor blockade on voluntary ethanol consumption. Since length of ethanol access period can influence ethanol consumption levels as well as potential pharmacological effects in such studies, the present study was conducted to determine the effects of acute administration of the glucocorticoid receptor (GR) antagonist mifepristone on voluntary ethanol intake under limited access conditions. Rats were fluid restricted and given concurrent access to 10% ethanol and water in a two-bottle choice paradigm for 1 h/day, 5 days a week. Both fluids were available ad libitum during the remaining 2 days per week. Administration of mifepristone (1, 5 and 20 mg/kg i.p.) immediately prior to the limited access two-bottle access period dose-dependently suppressed ethanol intake (maximum 40% at 20 mg/kg). The mineralcorticoid receptor (MR) antagonist spironolactone (10, 25 and 50 mg/kg i.p.) was without effect on ethanol intake, and neither compound had an effect on water intake. These data confirm an active role of GRs in modulating voluntary ethanol consumption, particularly under conditions of limited access.
有大量证据表明类固醇激素，尤其是肾上腺糖皮质激素，对乙醇摄入量有控制作用。然而，迄今为止，采用药理学方法的研究未能发现糖皮质激素受体阻断对自愿乙醇消费的影响。由于在这类研究中，乙醇获取期的长度会影响乙醇消费水平以及潜在的药理学效应，因此本研究旨在确定在有限获取条件下急性给予糖皮质激素受体（GR）拮抗剂米非司酮对自愿乙醇摄入量的影响。大鼠进行液体限制，并在两瓶装选择范式中，每天1小时、每周5天同时给予10%乙醇和水。每周其余2天，两种液体均可随意获取。在有限获取两瓶装阶段之前立即腹腔注射米非司酮（1、5和20毫克/千克）剂量依赖性地抑制乙醇摄入量（20毫克/千克时最大抑制40%）。盐皮质激素受体（MR）拮抗剂螺内酯（10、25和50毫克/千克腹腔注射）对乙醇摄入量无影响，且两种化合物对水摄入量均无影响。这些数据证实了GRs在调节自愿乙醇消费中发挥积极作用，尤其是在有限获取条件下。
