Besheer Joyce, Frisbee Suzanne, Randall Patrick A, Jaramillo Anel A, Masciello Maria
Bowles Center for Alcohol Studies, USA; Curriculum in Neurobiology, USA; Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
Bowles Center for Alcohol Studies, USA.
Neuropharmacology. 2016 Feb;101:216-24. doi: 10.1016/j.neuropharm.2015.09.027. Epub 2015 Sep 28.
Gabapentin, a drug used in the treatment of epileptic seizures and neuropathic pain, has shown efficacy in the treatment of alcohol dependence. Moreover, given that gabapentin is used in the general population (e.g., non-dependent individuals, social drinkers), we sought to utilize preclinical assessments to examine the effects of gabapentin on sensitivity to moderate alcohol doses and alcohol self-administration in rats with a history of moderate drinking. To this end, we assessed whether gabapentin (0, 10, 30, 120 mg/kg, IG) pretreatment alters sensitivity to experimenter- and self-administered alcohol, and whether gabapentin alone has alcohol-like discriminative stimulus effects in rats trained to discriminate alcohol dose (1 g/kg, IG) vs. water. Second, we assessed whether gabapentin (0, 10, 30, 60 mg/kg, IG) would alter alcohol self-administration. Gabapentin pretreatment potentiated the interoceptive effects of both experimenter-administered and self-administered alcohol in discrimination-trained rats. Additionally, the highest gabapentin doses tested (30 and 120 mg/kg) were found to have partial alcohol-like discriminative stimulus effects when administered alone (e.g., without alcohol). In the self-administration trained rats, gabapentin pretreatment (60 mg/kg) resulted in an escalation in alcohol self-administration. Given the importance of interoceptive drug cues in priming and maintaining self-administration, these data define a specific behavioral mechanism (i.e., potentiation of alcohol effects) by which gabapentin may increase alcohol self-administration in non-dependent populations.
加巴喷丁是一种用于治疗癫痫发作和神经性疼痛的药物，已显示出对酒精依赖治疗有效。此外，鉴于加巴喷丁在普通人群（如非依赖个体、社交饮酒者）中使用，我们试图利用临床前评估来检查加巴喷丁对中度饮酒史大鼠对中度酒精剂量的敏感性和酒精自我给药的影响。为此，我们评估了加巴喷丁（0、10、30、120毫克/千克，灌胃）预处理是否会改变对实验者给予和自我给药酒精的敏感性，以及单独使用加巴喷丁在经过训练以区分酒精剂量（1克/千克，灌胃）与水的大鼠中是否具有类似酒精的辨别刺激作用。其次，我们评估了加巴喷丁（0、10、30、60毫克/千克，灌胃）是否会改变酒精自我给药。加巴喷丁预处理增强了辨别训练大鼠中实验者给予和自我给药酒精的内感受作用。此外，测试的最高加巴喷丁剂量（30和120毫克/千克）单独给药时（如无酒精）被发现具有部分类似酒精的辨别刺激作用。在自我给药训练的大鼠中，加巴喷丁预处理（60毫克/千克）导致酒精自我给药增加。鉴于内感受性药物线索在引发和维持自我给药中的重要性，这些数据定义了一种特定的行为机制（即增强酒精作用），通过该机制加巴喷丁可能会增加非依赖人群中的酒精自我给药。
