Kulkosky P J, Sanchez M R, Foderaro M A, Chiu N
Department of Psychology, University of Southern Colorado, Pueblo 81001-4901.
Alcohol. 1989 Sep-Oct;6(5):395-402. doi: 10.1016/0741-8329(89)90010-4.
Release of the brain-gut peptide cholecystokinin (CCK) is stimulated by intragastric instillation of ethanol, and peripheral administration of CCK inhibits ethanol consumption. To assess the temporal specificity of the inhibitory effect of CCK on alcohol intake, water-deprived rats were given 5% ethanol at 20, 10 or 0 min after intraperitoneal injections of CCK octapeptide. Delaying access to ethanol for 20 min prevented a significant effect of CCK on intake. CCK's temporally constrained inhibitory action on alcohol consumption is consistent with an ethanol satiation effect. To test the motivational specificity of CCK's effect on fluid intake, rats were allowed a 2-bottle choice of 2% ethanol and water after CCK injections. Ethanol solution intake was suppressed by CCK, and total water intake was unaffected. The putative alcohol satiation action of CCK is appropriately specific to ethanol solution in free-choice tests. Hungry, but not fluid-deprived rats that were either ethanol experienced or naive received a 2-bottle choice of 4% ethanol or water after CCK or saline injections. CCK again specifically inhibited ethanol intake, but this effect required prior ethanol experience. Doses of CCK and naloxone, an opioid receptor blocker, combined to inhibit ethanol intake in an infra-dose-additive manner in water-deprived rats. CCK may act endogenously, in part on opioid receptor-mediated processes, as a preabsorptive satiety signal of ethanol. The full expression of this action appears to depend on prior conditioning of nutritive expectancy of the postingestive effects of alcohol.
胃内灌注乙醇可刺激脑肠肽胆囊收缩素（CCK）的释放，而外周给予CCK可抑制乙醇摄入。为评估CCK对酒精摄入抑制作用的时间特异性，给缺水大鼠腹腔注射CCK八肽后20、10或0分钟给予5%乙醇。将获取乙醇的时间推迟20分钟可防止CCK对摄入量产生显著影响。CCK对酒精消费的时间受限抑制作用与乙醇饱足效应一致。为测试CCK对液体摄入影响的动机特异性，给大鼠注射CCK后让其在2%乙醇和水之间进行双瓶选择。CCK抑制了乙醇溶液的摄入，而总水摄入量未受影响。在自由选择测试中，CCK假定的酒精饱足作用对乙醇溶液具有适当的特异性。经历过乙醇或未经历过乙醇的饥饿但未缺水的大鼠在注射CCK或生理盐水后，在4%乙醇和水之间进行双瓶选择。CCK再次特异性抑制乙醇摄入，但这种作用需要先前有乙醇经历。在缺水大鼠中，CCK和阿片受体阻滞剂纳洛酮的剂量联合以亚剂量相加的方式抑制乙醇摄入。CCK可能作为乙醇的一种吸收前饱足信号内源性地发挥作用，部分作用于阿片受体介导的过程。这种作用的充分表达似乎取决于先前对酒精摄入后效应的营养预期的条件作用。
