Stromberg Michael F
Center For Studies of Addiction, Department of Psychiatry, University of Pennsylvania, Philadelphia, PA 19104, USA.
Pharmacol Biochem Behav. 2004 Aug;78(4):743-50. doi: 10.1016/j.pbb.2004.05.006.
Naltrexone has been evaluated in preclinical animal models of ethanol consumption and found to be effective in most reports. In clinical use, naltrexone has not proved to be as efficacious in preventing relapse. While naltrexone targets opioid receptors, many other neurotransmitter systems are targeted by ethanol and, to a greater or lesser extent, contribute to modulating ethanol's reinforcing effects. There has been indication that drugs active at the gamma amino butyric acid B (GABAB) receptors can affect the self-administration of many drugs with abuse potential. The experiments reported here evaluated the effect of three doses of baclofen (2.5, 5.0, or 7.5 mg/kg), a GABAB agonist, administered alone or in combination with a single dose of naltrexone (1.0 mg/kg). In Experiment 1, both naltrexone and baclofen, at the two higher doses tested, significantly reduced ethanol consumption in Wistar rats using a limited access procedure on Drug Days 1 and 2. When combined on Drug Days 3 and 4, baclofen/naltrexone was significantly more effective in reducing ethanol consumption than did either drug alone. Neither drug, alone or in combination, had an effect on water consumption. In Experiment 2, both baclofen and naltrexone again significantly reduced ethanol consumption, with no evidence that chronic administration across Drug Days 3 and 4 further reduced consumption compared with Drug Days 1 and 2. The clinical use of multiple pharmacotherapeutic agents in combination may allow for the use of lower doses of individual components, thereby reducing the negative side effects that contribute to lower compliance and higher relapse.
纳曲酮已在乙醇消费的临床前动物模型中进行了评估，并且在大多数报告中被发现是有效的。在临床应用中，纳曲酮在预防复发方面尚未被证明具有同样的疗效。虽然纳曲酮作用于阿片受体，但乙醇还作用于许多其他神经递质系统，并且在或多或少的程度上有助于调节乙醇的强化作用。有迹象表明，对γ-氨基丁酸B（GABAB）受体有活性的药物可以影响许多具有滥用潜力的药物的自我给药。本文报道的实验评估了三种剂量的巴氯芬（2.5、5.0或7.5毫克/千克）单独给药或与单剂量纳曲酮（1.0毫克/千克）联合给药的效果。在实验1中，在药物第1天和第2天使用有限接触程序，纳曲酮和两种较高测试剂量的巴氯芬均显著降低了Wistar大鼠的乙醇消费量。在药物第3天和第4天联合使用时，巴氯芬/纳曲酮在降低乙醇消费方面比单独使用任何一种药物都更有效。单独或联合使用这两种药物对水的消费量均无影响。在实验2中，巴氯芬和纳曲酮再次显著降低了乙醇消费量，没有证据表明与药物第1天和第2天相比，在药物第3天和第4天进行慢性给药会进一步降低消费量。联合使用多种药物治疗剂的临床应用可能允许使用较低剂量的各个成分，从而减少导致依从性降低和复发率升高的负面副作用。
