Schwarz-Stevens K S, Files F J, Samson H H
Alcohol and Drug Abuse Institute, University of Washington, Seattle.
Alcohol Clin Exp Res. 1992 Aug;16(4):822-32. doi: 10.1111/j.1530-0277.1992.tb00686.x.
In the following series of experiments, effects of morphine (0.1, 0.3, 1.0, 3.0, and 10.0 mg/kg) and naloxone (0.1, 0.3, and 1.0 mg/kg) were assessed in nondeprived rats trained to leverpress with 10% ethanol, sweetened ethanol, or 5% sucrose and water as the reinforcers. Morphine, at doses of 0.1, 0.3, and 1.0 mg/kg had little effect on responding with ethanol or sweetened ethanol available on a fixed ratio 4 (FR4) schedule of reinforcement, but at the 3.0 mg/kg dose, morphine suppressed responding to near zero. Similar results were obtained when 10% ethanol and water were available on a concurrent FR4 FR4 schedule of reinforcement. When 5% sucrose and water were available concurrently, morphine suppressed responding at 3.0 and 10 mg/kg. Naloxone (0.1, 0.3, and 1.0 mg/kg) decreased responding for ethanol, sweetened ethanol, and sucrose solutions in a dose-dependent manner. Naloxone decreased total number of responses/session by shortening the duration of responding without affecting momentary rate. Overall, the data suggest that the endogenous opioid system plays a role in the ability of ethanol to reinforce operant behavior. However, this role does not appear to be specific to ethanol because similar results were observed with sucrose reinforcement. Failure to find enhanced ethanol intakes following morphine injections in the operant situation suggests that the method used to measure ethanol self-administration makes a difference in assessing the effects of drugs on ethanol intake.
在以下一系列实验中,对未禁食的大鼠进行了评估,这些大鼠经训练后以10%乙醇、甜味乙醇或5%蔗糖和水作为强化物进行杠杆按压。吗啡(0.1、0.3、1.0、3.0和10.0毫克/千克)和纳洛酮(0.1、0.3和1.0毫克/千克)的作用在固定比率4(FR4)强化程序下,0.1、0.3和1.0毫克/千克剂量的吗啡对以乙醇或甜味乙醇为强化物时的反应影响不大,但在3.0毫克/千克剂量时,吗啡将反应抑制至接近零。当在同时进行的FR4 FR4强化程序中提供10%乙醇和水时,也得到了类似结果。当同时提供5%蔗糖和水时,吗啡在3.0和10毫克/千克剂量下抑制反应。纳洛酮(0.1、0.3和1.0毫克/千克)以剂量依赖性方式减少对乙醇、甜味乙醇和蔗糖溶液的反应。纳洛酮通过缩短反应持续时间而不影响瞬间速率来减少每次实验的总反应次数。总体而言,数据表明内源性阿片系统在乙醇强化操作性行为的能力中起作用。然而,这一作用似乎并非乙醇所特有,因为在蔗糖强化时也观察到了类似结果。在操作性实验中未发现吗啡注射后乙醇摄入量增加,这表明用于测量乙醇自我给药的方法在评估药物对乙醇摄入量的影响方面存在差异。