Czachowski Cristine L, Legg Brooke H, Stansfield Kirstie H
Center for Alcohol and Addiction Studies, Brown University, Providence, Rhode Island 02912, USA.
Alcohol Clin Exp Res. 2006 May;30(5):812-8. doi: 10.1111/j.1530-0277.2006.00094.x.
Baclofen, a GABA(B) agonist, has been found to decrease alcohol craving in humans and to nonselectively decrease ethanol intake in some rodent models. This experiment assessed the effects of repeated administration of baclofen on reinforcer seeking and consumption using the sipper tube appetitive/consummatory model of ethanol access.
Subjects were divided into 2 groups and trained to make 30 lever press responses that resulted in access to either 10% ethanol or 2% sucrose in a sipper tube-drinking spout for 20 minutes. Three doses of baclofen were tested (0.3, 1.0, and 3.0 mg/kg) and each drug treatment was assessed using the following schedule: Monday, saline; Tuesday to Thursday, baclofen; and Friday, saline.
The low dose of baclofen had no effect on the seeking or intake of either sucrose or ethanol, and the 1.0 mg/kg dose also had no effect on the appetitive, seeking response. However, the 1.0 mg/kg dose significantly decreased sucrose intake (from an average of 0.56 to 0.41 g/kg) and significantly increased ethanol intake (from an average of 0.77 to 1.00 g/kg). Similarly, the high dose (3.0 mg/kg) decreased sucrose intake and had a tendency to increase ethanol intake while decreasing both sucrose seeking and ethanol seeking.
Overall, baclofen treatment affected reinforcer intake at doses that had no effect on reinforcer seeking, and effective doses decreased both sucrose seeking and ethanol seeking. Moreover, the effects on reinforcer intake were disparate, in that baclofen increased ethanol drinking and decreased sucrose drinking. The nonspecific effects of baclofen suggest that the GABA(B) system may be involved in general consummatory or drinking behaviors and does not appear to specifically regulate ethanol-motivated responding.
巴氯芬是一种γ-氨基丁酸B(GABA(B))激动剂,已发现其可降低人类对酒精的渴望,并在一些啮齿动物模型中能非选择性地减少乙醇摄入量。本实验使用吸管式乙醇获取的摄食/ consummatory模型,评估了重复给予巴氯芬对强化物寻求和消费的影响。
将实验对象分为两组,并训练其进行30次杠杆按压反应,以在吸管式饮水口获取10%乙醇或2%蔗糖,持续20分钟。测试了三种剂量的巴氯芬(0.3、1.0和3.0毫克/千克),每种药物治疗按以下时间表进行评估:周一,生理盐水;周二至周四,巴氯芬;周五,生理盐水。
低剂量的巴氯芬对蔗糖或乙醇的寻求或摄入量均无影响,1.0毫克/千克剂量对摄食性寻求反应也无影响。然而,1.0毫克/千克剂量显著降低了蔗糖摄入量(从平均0.56克/千克降至0.41克/千克),并显著增加了乙醇摄入量(从平均0.77克/千克增至1.00克/千克)。同样,高剂量(3.0毫克/千克)降低了蔗糖摄入量,并有增加乙醇摄入量的趋势,同时减少了蔗糖寻求和乙醇寻求。
总体而言,巴氯芬治疗在对强化物寻求无影响的剂量下影响了强化物摄入量,有效剂量减少了蔗糖寻求和乙醇寻求。此外,对强化物摄入量的影响是不同的,因为巴氯芬增加了乙醇饮用量而减少了蔗糖饮用量。巴氯芬的非特异性作用表明,GABA(B)系统可能参与一般的摄食或饮水行为,似乎并未特异性调节由乙醇驱动的反应。