Lê A D, Poulos C X, Harding S, Watchus J, Juzytsch W, Shaham Y
Biobehavioral Research Department, Center for Addiction and Mental Health, Toronto, Ontario, Canada.
Neuropsychopharmacology. 1999 Sep;21(3):435-44. doi: 10.1016/S0893-133X(99)00024-X.
We have recently shown that priming injections of alcohol and footshock stress reinstate alcohol seeking in drug-free rats. Here we tested whether naltrexone and fluoxetine, two drugs used in the treatment of alcohol dependence, would affect reinstatement of alcohol seeking induced by these events. We also determined the effects of these drugs on alcohol self-administration during the maintenance phase. Rats were trained to press a lever for a 12% w/v alcohol solution. After stable drug-taking behavior was obtained, lever pressing for alcohol was extinguished. Reinstatement of drug seeking was then determined after priming injections of alcohol (0.24-0.96 g/kg) or exposure to intermittent footshock (5 and 15 min). Rats were pretreated with naltrexone (0.2-0.4 mg/kg) or fluoxetine (2.5-5 mg/kg) during maintenance or during tests for reinstatement. Both naltrexone and fluoxetine decreased lever presses for alcohol during the maintenance phase. Naltrexone blocked alcohol-induced, but not stress-induced reinstatement. In contrast, fluoxetine blocked stress-induced reinstatement, while its effect on alcohol-induced reinstatement was less consistent. The implications of these data to the understanding of relapse to alcohol are discussed.
我们最近发现，预先注射酒精和足部电击应激会使未接触毒品的大鼠恢复觅酒行为。在此，我们测试了用于治疗酒精依赖的两种药物纳曲酮和氟西汀是否会影响由这些事件诱导的觅酒行为恢复。我们还确定了这些药物在维持阶段对酒精自我给药的影响。大鼠被训练按压杠杆以获取12%（w/v）的酒精溶液。在获得稳定的服药行为后，停止按压杠杆获取酒精。然后在预先注射酒精（0.24 - 0.96 g/kg）或暴露于间歇性足部电击（5分钟和15分钟）后，确定觅药行为的恢复情况。在维持阶段或恢复测试期间，大鼠用纳曲酮（0.2 - 0.4 mg/kg）或氟西汀（2.5 - 5 mg/kg）进行预处理。纳曲酮和氟西汀在维持阶段均减少了按压杠杆获取酒精的行为。纳曲酮阻断了酒精诱导的，但未阻断应激诱导的恢复。相比之下，氟西汀阻断了应激诱导的恢复，而其对酒精诱导的恢复的影响则不太一致。本文讨论了这些数据对理解酒精复吸的意义。
