Combination pharmacotherapy: a mixture of small doses of naltrexone, fluoxetine, and a thyrotropin-releasing hormone analogue reduces alcohol intake in three strains of alcohol-preferring rats.
Combination pharmacotherapy: a mixture of small doses of naltrexone, fluoxetine, and a thyrotropin-releasing hormone analogue reduces alcohol intake in three strains of alcohol-preferring rats.
复制标题
联合药物疗法：小剂量纳曲酮、氟西汀和促甲状腺激素释放激素类似物的混合物可减少三种嗜酒大鼠的酒精摄入量。
DOI：
10.1093/alcalc/35.1.76
复制
发表时间：
2000
期刊：
影响因子：
--
通讯作者：
Yang,Y
中科院分区：
文献类型：
--
作者：
Rezvani,AH;Overstreet,DH;Mason,GA;Janowsky,DS;Hamedi,M;ClarkJr,E;Yang,Y
同时用一种以上的药物治疗某些疾病是很常见的。由于酒精寻求行为涉及多个神经递质系统，因此针对多个系统的治疗方法应该比针对单个系统的治疗方法更有效地减少酒精摄入量。为了验证这一假设，我们比较了低剂量的个别药物报告，以减少自愿饮酒的疗效，这些药物的混合物在相同的低剂量在减少酒精摄入量的三个品种的酒精偏好大鼠（P，HAD，和Fawn-Hooded）的疗效。在连续进入模式中建立酒精摄入的稳定基线后，每只大鼠在09：30接受单独的单次腹膜内注射相对低剂量的纳洛酮（2.0 mg/kg）、氟西汀（1.0 mg/kg）、促甲状腺素释放激素类似物TA-0910（0.2 mg/kg）、所有三种药物的混合物或溶媒。每只大鼠接受所有给药，注射间洗脱期至少为3天。在注射后6小时和24小时测量酒精和水的摄入量，并在24小时测量食物摄入量。我们的研究结果表明，个别药物并没有显着影响食物，水或酒精的摄入量。然而，混合物显着减少了所有三种菌株的酒精摄入量，但对食物摄入量没有影响。当HAD大鼠接受口服剂量的单个药物或混合物时，获得了类似的结果。当P大鼠连续10天腹腔注射该混合物时，有持续的抑制作用。这些研究结果表明，设计用于同时靶向多巴胺能、多巴胺能和阿片样物质能系统的联合治疗可以减少酒精摄入量，即使混合物中单个药物的剂量相对较低，并且在单独给药时无效。
It is common to treat some diseases with more than one medication simultaneously. Since more than one neurotransmitter system is involved in alcohol-seeking behaviour, then a therapeutic approach that targets more than one system should be more effective in reducing alcohol intake than one addressing a single system. To test this hypothesis, we compared the efficacy of low doses of individual drugs reported to reduce voluntary alcohol drinking to the efficacy of a mixture of these agents at the same low doses in reducing alcohol intake in three strains of alcohol-preferring rats (P, HAD, and Fawn-Hooded). After establishment of a stable baseline for alcohol intake in a continuous access paradigm, each rat received separate single i.p. injections of relatively low doses of either naltrexone (2.0 mg/kg), fluoxetine (1.0 mg/kg), the thyrotropin-releasing hormone analogue TA-0910 (0.2 mg/kg), a mixture of all three drugs, or the vehicle at 09:30. Each rat received all treatments, with an inter-injection washout period of at least 3 days. Alcohol and water intakes were measured at 6 and 24 h, and food intake was measured at 24 h, after the injection. Our results show that individual drugs did not significantly affect food, water, or alcohol intake. However, the mixture significantly reduced alcohol intake in all three strains, but had no effect on food intake. Similar results were obtained when the HAD rats received an oral dose of the individual drugs or the mixture. When P rats were given an i.p. injection of the mixture for 10 consecutive days, there was a continued suppressing effect. These findings show that a combination treatment designed to target simultaneously serotonergic, dopaminergic, and opioidergic systems can reduce alcohol intake, even though the doses of the individual drugs in the mixture are relatively low and ineffective when given singly.