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促甲状腺激素释放激素类似物TA-0910可抑制非洲绿猴的酒精摄入量。

Thyrotropin releasing hormone analog TA-0910 suppresses alcohol intake in alcohol drinking African green monkeys.

作者信息

Rezvani A H, Garbutt J C, Overstreet D H, Li L, Walker C H, Yang Y, Mason G A

机构信息

Skipper Bowles Center for Alcohol Studies, University of North Carolina School of Medicine at Chapel Hill, USA.

出版信息

Alcohol Clin Exp Res. 1997 Apr;21(2):261-6.

PMID:9113262
Abstract

In previous studies, we found that single injections of the thyrotropin-releasing hormone analog TA-0910 dose-dependently reduced alcohol intake and preference in alcohol-preferring (P) and Fawn-Hooded (FH) rats over a 24-hr period of continuous access to alcohol and water. However, several consecutive daily injections of TA-0910 resulted in the development of tolerance to these effects. In the present study, we found that in a 5-hr limited-access schedule in which monkeys could select an aqueous alcohol solution (7.5% v/v) or tap water, single doses of TA-0910 (0.0625, 0.125, 0.25, 0.5, and 0.75 mg/kg), similar to those found effective in P and FH rats, reduced consumption of alcohol. In this protocol, tolerance to the attenuating effects of TA-0910 on alcohol intake was not evident after five consecutive once-daily doses of 0.5 mg/kg. Furthermore, it was shown that a single dose of 0.75 mg/kg TA-0910 did not significantly influence 24-hr water intake when water was the only available fluid, but did reduce the intake of a preferred solution of saccharin. These findings suggest that activation of brain thyrotropin-releasing hormone systems reduces alcohol intake in primates and that tolerance to this effect is not evident within 5 days under a limited access schedule.

摘要

在先前的研究中,我们发现,在持续接触酒精和水24小时的期间,单次注射促甲状腺激素释放激素类似物TA - 0910能剂量依赖性地减少嗜酒(P)大鼠和小鹿斑头大鼠(FH)的酒精摄入量和偏爱程度。然而,连续几日注射TA - 0910会导致对这些效应产生耐受性。在本研究中,我们发现,在一个5小时的限时获取实验方案中,猴子可以选择酒精水溶液(7.5% v/v)或自来水,单剂量的TA - 0910(0.0625、0.125、0.25、0.5和0.75 mg/kg),与在P大鼠和FH大鼠中发现有效的剂量相似,能减少酒精的消耗量。在该实验方案中,连续五日每日一次注射0.5 mg/kg的TA - 0910后,对其减少酒精摄入的衰减效应并未出现耐受性。此外,研究表明,当仅提供水作为唯一可获取的液体时,单剂量0.75 mg/kg的TA - 0910不会显著影响24小时的水摄入量,但会减少对糖精偏好溶液的摄入量。这些发现表明,激活大脑促甲状腺激素释放激素系统可减少灵长类动物的酒精摄入量,并且在限时获取实验方案下,5天内对这种效应的耐受性并不明显。

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