Randall Patrick A, Jaramillo Anel A, Frisbee Suzanne, Besheer Joyce
Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Thurston-Bowles Building; CB#7178, Chapel Hill, NC, 27599, USA.
Psychopharmacology (Berl). 2015 Jul;232(14):2443-54. doi: 10.1007/s00213-015-3878-1. Epub 2015 Feb 7.
Varenicline, a smoking-cessation agent, may be useful in treating alcohol use disorders. An important consideration when studying factors that influence drinking/relapse is influence of the pharmacological effects of alcohol on these behaviors. Pre-exposure to alcohol (priming) can increase craving, drinking, and seeking behaviors.
The primary goal of this work was to determine the effects of varenicline on alcohol-primed self-administration and seeking behavior in male Long-Evans rats.
First, we assessed whether varenicline (0, 0.3, 1, 3 mg/kg, IP) has alcohol-like discriminative stimulus effects and whether varenicline alters sensitivity to alcohol in rats trained to discriminate a moderate alcohol dose (1 g/kg, IG) vs. water. Second, animals trained to self-administer alcohol underwent assessments to test the effects of: (i) varenicline (0, 0.3, 1, 3 mg/kg, IP) on self-administration, (ii) alcohol priming (0, 0.3, 1 g/kg, IG) on self-administration and seeking behavior, and (iii) varenicline (1 mg/kg) in combination with alcohol priming (1 g/kg) on these behaviors.
Varenicline did not substitute for alcohol but disrupted the expression of sensitivity to alcohol. Varenicline decreased self-administration but only at a motor-impairing dose (3 mg/kg). Alcohol priming decreased self-administration and seeking behavior. Varenicline (1 mg/kg) blocked this effect under self-administration conditions, but not seeking conditions, which effectively resulted in increased alcohol intake.
These findings suggest the importance of further behavioral and mechanistic studies to evaluate the use of varenicline in treating alcohol use disorders and its potential impact on drinking patterns in smokers using varenicline as a smoking-cessation aid.
伐尼克兰是一种戒烟药物，可能对治疗酒精使用障碍有用。在研究影响饮酒/复发的因素时，一个重要的考虑因素是酒精的药理作用对这些行为的影响。预先接触酒精（启动）会增加渴望、饮酒和觅酒行为。
这项研究的主要目标是确定伐尼克兰对雄性长 Evans 大鼠酒精启动的自我给药和觅酒行为的影响。
首先，我们评估伐尼克兰（0、0.3、1、3 毫克/千克，腹腔注射）是否具有类似酒精的辨别刺激作用，以及伐尼克兰是否会改变训练用于辨别中等酒精剂量（1 克/千克，灌胃）与水的大鼠对酒精的敏感性。其次，训练用于自我给药酒精的动物接受评估，以测试以下各项的影响：（i）伐尼克兰（0、0.3、1、3 毫克/千克，腹腔注射）对自我给药的影响，（ii）酒精启动（0、0.3、1 克/千克，灌胃）对自我给药和觅酒行为的影响，以及（iii）伐尼克兰（1 毫克/千克）与酒精启动（1 克/千克）联合使用对这些行为的影响。
伐尼克兰不能替代酒精，但会破坏对酒精敏感性的表达。伐尼克兰减少自我给药，但仅在运动损害剂量（3 毫克/千克）时。酒精启动减少自我给药和觅酒行为。在自我给药条件下，伐尼克兰（1 毫克/千克）阻断了这种作用，但在觅酒条件下未阻断，这实际上导致酒精摄入量增加。
这些发现表明，进一步开展行为和机制研究以评估伐尼克兰在治疗酒精使用障碍中的应用及其对使用伐尼克兰作为戒烟辅助手段的吸烟者饮酒模式的潜在影响具有重要意义。
