Hauser Sheketha R, Wilden Jessica A, Deehan Gerald A, McBride William J, Rodd Zachary A
Department of Psychiatry, Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis, Indiana.
Alcohol Clin Exp Res. 2014 Oct;38(10):2678-86. doi: 10.1111/acer.12540.
The results of several studies suggest that there may be common neurocircuits regulating drug-seeking behaviors. Common biological pathways regulating drug-seeking would explain the phenomenon that seeking for 1 drug can be enhanced by exposure to another drug of abuse. The objective of this study was to assess the time course effects of acute cocaine administration on ethanol (EtOH) seeking and relapse.
Alcohol-preferring (P) rats were allowed to self-administer 15% EtOH and water. EtOH-seeking was assessed through the use of the Pavlovian spontaneous recovery (PSR) model, while EtOH-relapse drinking was assessed through the use of the alcohol-deprivation effect.
Cocaine (0, 1, or 10 mg/kg), injected immediately, 30 minutes, or 4 hours prior to the first PSR testing session, dose-dependently increased responding on the EtOH lever compared to extinction responses and responding by saline controls. Under relapse conditions, cocaine given immediately prior to the relapse session had no effect (1 mg/kg) or reduced responding (10 mg/kg). In contrast, cocaine given 4 hours prior to the relapse session markedly enhanced EtOH responding compared to saline.
The enhanced expression of EtOH-seeking and EtOH-relapse behaviors may be a result of a priming effect of cocaine on neuronal circuits mediating these behaviors. The effect of cocaine on EtOH-relapse drinking is indicative of the complex interactions that can occur between drugs of abuse; production of conflicting behaviors (immediate), and priming of relapse/seeking (4-hour delay).
多项研究结果表明,可能存在调节觅药行为的共同神经回路。调节觅药行为的共同生物学途径可以解释这样一种现象,即接触另一种滥用药物可增强对一种药物的觅求。本研究的目的是评估急性给予可卡因对乙醇(EtOH)觅求及复吸的时程效应。
给予嗜酒(P)大鼠自行摄取15%的EtOH和水。通过巴甫洛夫式自发恢复(PSR)模型评估EtOH觅求,而通过酒精剥夺效应评估EtOH复吸饮酒情况。
在首次PSR测试 session 前即刻、30分钟或4小时注射可卡因(0、1或10mg/kg),与消退反应及生理盐水对照组的反应相比,可以剂量依赖性地增加EtOH杠杆上的反应。在复吸条件下,在复吸session前即刻给予可卡因无作用(1mg/kg)或减少反应(10mg/kg)。相比之下,在复吸session前4小时给予可卡因与生理盐水相比,显著增强了EtOH反应。
EtOH觅求及EtOH复吸行为的增强表达可能是可卡因对介导这些行为的神经回路产生启动效应的结果。可卡因对EtOH复吸饮酒的影响表明滥用药物之间可能发生复杂的相互作用;产生冲突行为(即刻)以及启动复吸/觅求(4小时延迟)。