Tomkins D M, Le A D, Sellers E M
Addiction Research Foundation, Toronto, Ontario, Canada.
Psychopharmacology (Berl). 1995 Feb;117(4):479-85. doi: 10.1007/BF02246222.
The effect of the 5-HT3 antagonist ondansetron on ethanol self-administration was examined in a limited access paradigm. Acute administration of ondansetron (0.01 and 0.1 mg/kg) reduced ethanol intake in male Wistar rats by 35%, whilst water intake was unaffected. Both a lower (0.001 mg/kg) and higher dose (1 mg/kg) of ondansetron failed to modify ethanol consumption. Ondansetron did not, however, alter the pharmacokinetic profile of an orally administered dose of ethanol (1 g/kg) over the same dose range. To examine the generality of these findings and to determine if tolerance would develop to the suppressant effects of ondansetron on ethanol intake, male C57BL/6 mice were treated with ondansetron (0.001, 0.01 and 0.1 mg/kg) over 22 days, 30 min prior to scheduled access to ethanol. Both 0.01 and 0.1 mg/kg doses reduced ethanol intake; however, water intake was not altered by either dose. This finding confirms and extends the generality of the effects of 5-HT3 receptor antagonists on ethanol intake across different species and different paradigms of ethanol consumption. More importantly, the present study shows that the reduction in ethanol intake induced by ondansetron was maintained even after a prolonged period of treatment and is not due to an alteration in the absorption or metabolism of ethanol.
在有限接触范式中研究了5-羟色胺3（5-HT3）拮抗剂昂丹司琼对乙醇自我给药的影响。急性给予昂丹司琼（0.01和0.1毫克/千克）可使雄性Wistar大鼠的乙醇摄入量减少35%，而水摄入量未受影响。较低剂量（0.001毫克/千克）和较高剂量（1毫克/千克）的昂丹司琼均未能改变乙醇消耗量。然而，在相同剂量范围内，昂丹司琼并未改变口服剂量乙醇（1克/千克）的药代动力学特征。为了检验这些发现的普遍性，并确定是否会对昂丹司琼对乙醇摄入的抑制作用产生耐受性，在预定接触乙醇前30分钟，对雄性C57BL/6小鼠用昂丹司琼（0.001、0.01和0.1毫克/千克）进行了22天的治疗。0.01和0.1毫克/千克剂量均降低了乙醇摄入量；然而，两种剂量均未改变水摄入量。这一发现证实并扩展了5-HT3受体拮抗剂对不同物种和不同乙醇消费范式下乙醇摄入影响的普遍性。更重要的是，本研究表明，即使经过长时间治疗，昂丹司琼诱导的乙醇摄入量减少仍持续存在，且不是由于乙醇吸收或代谢的改变所致。
