Bell S M, Reynolds J G, Thiele T E, Gan J, Figlewicz D P, Woods S C
University of Washington, Department of Psychology, Seattle 98195, USA.
Psychopharmacology (Berl). 1998 Sep;139(1-2):128-35. doi: 10.1007/s002130050697.
Corticotropin releasing factor (CRF), a neuropeptide secreted by hypothalamic and extrahypothalamic neurons, is thought to mediate stress-related behaviors. The tension reduction hypothesis suggests that ethanol drinking reduces stress; that drinking is reinforced by this reduced stress; and that the probability of drinking therefore subsequently increases. CRF also decrease food intake, and might decrease ethanol drinking similarly. We addressed these hypotheses directly by assessing the effects of intracerebroventricular (i.c.v.) CRF upon ethanol drinking (1 h/day). Rats were provided drinking tubes containing ethanol solutions that were gradually incremented in concentration (from 2% to 8% w/v, over 38 days). Ethanol intakes remained stable, ranging from 0.4 to 0.5 g/kg per hour on average, and a two-bottle choice test revealed that ethanol was preferred reliably to water. Third-i.c.v. cannulae were surgically implanted and CRF or vehicle was acutely injected immediately prior to the sessions. CRF dose-dependently reduced ethanol intake by 31% (0.5 microg) and 64% (5.0 microg), and reduced 24-h food by 9% and 21%, respectively, but did not alter body weights. I.c.v. CRF reduced ethanol drinking despite any acute stress-like effects that may have been present. Hence, these data are inconsistent with the tension reduction hypothesis. On the other hand, our results support the concept that food intake and ethanol drinking may be mediated by similar mechanisms.
促肾上腺皮质激素释放因子(CRF)是一种由下丘脑和下丘脑外神经元分泌的神经肽,被认为可介导与应激相关的行为。紧张缓解假说认为,饮酒可以减轻压力;这种压力减轻会强化饮酒行为;因此随后饮酒的可能性会增加。CRF还会减少食物摄入量,可能同样会减少饮酒量。我们通过评估脑室内(i.c.v.)注射CRF对饮酒量(每天1小时)的影响来直接验证这些假说。为大鼠提供装有乙醇溶液的饮水管,乙醇溶液浓度在38天内逐渐增加(从2%到8% w/v)。乙醇摄入量保持稳定,平均每小时为0.4至0.5 g/kg,双瓶选择试验表明大鼠可靠地偏好乙醇而非水。通过手术植入第三脑室插管,在实验前立即急性注射CRF或赋形剂。CRF剂量依赖性地使乙醇摄入量减少了31%(0.5微克)和64%(5.0微克),使24小时食物摄入量分别减少了9%和21%,但未改变体重。尽管可能存在任何急性应激样效应,脑室内注射CRF仍减少了乙醇饮用量。因此,这些数据与紧张缓解假说不一致。另一方面,我们的结果支持食物摄入量和乙醇饮用量可能由相似机制介导的概念。