Mason G A, Rezvani A H, Overstreet D H, Garbutt J C
Skipper Bowles Center for Alcohol Studies, School of Medicine, University of North Carolina at Chapel Hill, USA.
Alcohol Clin Exp Res. 1996 Sep;20(6):1000-3. doi: 10.1111/j.1530-0277.1996.tb01937.x.
We previously reported that single intraperitoneal injections of the thyrotropin-releasing hormone analog TA-0910 dose-dependently reduce alcohol intake in alcohol-preferring (P) rats in a free-choice continuous access protocol. We later showed, using the same protocol, that a transient tolerance develops to this effect after several consecutive, once-daily injections. In the present study, P rats that had been accustomed to continuous access to alcohol were acclimated to a limited scheduled access protocol in which alcohol was available only between 10 and 11 AM. This resulted in an elevated rate of alcohol intake. Rats were then injected once daily with TA-0910 (0.75 mg/kg) or an equal volume of a saline vehicle at 9:45 AM for 12 consecutive days. After 11 days of scheduled access, rats were allowed continuous access to alcohol. Intake of alcohol and water was measured each day at 11:00 AM. Compared with vehicle, TA-0910 reduced alcohol intake on the 11 days of scheduled access and during the first hour of day 12 when continuous access was restored, but did not reduce total (24 hr) alcohol intake on day 12. Data from this experiment show that TA-0910 reduces alcohol intake over a long period of time in a limited scheduled access protocol.
我们之前报道过,在自由选择连续获取酒精的实验方案中,单次腹腔注射促甲状腺激素释放激素类似物TA-0910可使偏爱酒精的(P)大鼠的酒精摄入量呈剂量依赖性减少。后来我们使用相同的实验方案表明,在连续每日注射数次后,会对这种效应产生短暂耐受性。在本研究中,已经习惯连续获取酒精的P大鼠适应了有限的定时获取方案,即仅在上午10点至11点之间可获取酒精。这导致酒精摄入量增加。然后在上午9:45每天给大鼠注射一次TA-0910(0.75毫克/千克)或等体积的生理盐水载体,连续注射12天。在定时获取酒精11天后,让大鼠连续获取酒精。每天上午11:00测量酒精和水的摄入量。与载体相比,TA-0910在定时获取酒精的11天以及恢复连续获取酒精的第12天的第一个小时内减少了酒精摄入量,但在第12天并未减少总的(24小时)酒精摄入量。该实验数据表明,在有限的定时获取方案中,TA-0910可在很长一段时间内减少酒精摄入量。