Area de Psicobiologia, Universitat Jaume I, Avenida Sos Baynat s/n, 12071, Castellón, Spain.
Psychopharmacology (Berl). 2013 Apr;226(4):673-85. doi: 10.1007/s00213-012-2831-9. Epub 2012 Aug 11.
Hydrogen peroxide (H2O2) is the co-substrate used by catalase to metabolize ethanol to acetaldehyde in the brain. This centrally formed acetaldehyde has been involved in several ethanol-related behaviors.
The present research evaluated the effect of the H2O2 scavenger, alpha lipoic acid (LA), on the acquisition and reconditioning of ethanol-induced conditioned place preference (CPP).
Mice received pairings of a distinctive floor stimulus (CS+) associated with intraperitoneal injections of ethanol (2.5 g/kg). On alternate days, animals received pairings of a different floor stimulus (CS-) associated with saline injections. A different group of animals received pairings with the (CS-) associated with saline injections, and on alternate days they received LA (100 mg/kg) injected 30 min prior to ethanol (2.5 g/kg) administration paired with the (CS+). A preference test assessed the effect of LA on the acquisition of ethanol-induced CPP. A similar procedure was followed to study the effect of LA on the acquisition of cocaine- and morphine-induced CPP. A separate experiment evaluated the effect of LA on the reconditioning of ethanol-induced CPP. In addition, we investigated the consequence of LA administration on central H2O2 levels.
LA selectively blocked the acquisition of ethanol-induced CPP. Moreover, this compound impaired the reconditioning of ethanol-induced CPP. Additionally, we found that LA diminished H2O2 levels in the brain.
These data suggest that a decline in H2O2 availability by LA might impede the formation of brain ethanol-derived acetaldehyde by catalase, which results in an impairment of the rewarding properties of ethanol.
过氧化氢 (H2O2) 是过氧化氢酶代谢乙醇生成乙醛时的共底物。这种在中枢形成的乙醛与几种与乙醇相关的行为有关。
本研究评估了 H2O2 清除剂 α-硫辛酸 (LA) 对乙醇诱导的条件性位置偏爱 (CPP) 的获得和再条件作用的影响。
小鼠接受与腹腔注射乙醇 (2.5 g/kg) 相关的独特地板刺激 (CS+) 的配对。在其他日子里，动物接受与盐水注射相关的不同地板刺激 (CS-) 的配对。另一组动物接受与盐水注射相关的 (CS-) 的配对，并且在其他日子里，他们在接受与 (CS+) 相关的乙醇 (2.5 g/kg) 给药之前 30 分钟接受 LA (100 mg/kg) 注射。偏好测试评估了 LA 对乙醇诱导的 CPP 获得的影响。遵循类似的程序来研究 LA 对可卡因和吗啡诱导的 CPP 获得的影响。一个单独的实验评估了 LA 对乙醇诱导的 CPP 再条件作用的影响。此外，我们研究了 LA 给药对中枢 H2O2 水平的影响。
LA 选择性地阻断了乙醇诱导的 CPP 的获得。此外，这种化合物损害了乙醇诱导的 CPP 的再条件作用。此外，我们发现 LA 降低了大脑中的 H2O2 水平。
这些数据表明，LA 降低 H2O2 可用性可能会阻碍过氧化氢酶代谢乙醇生成脑乙醛，从而导致乙醇的奖赏特性受损。
