Ferreira Frederico R, Biojone Caroline, Joca Sâmia R L, Guimarães Francisco S
Department of Pharmacology, School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.
Behav Pharmacol. 2008 Oct;19(7):747-50. doi: 10.1097/FBP.0b013e3283123c98.
Oxidative stress disturbances have been reported in depressed patients and in animals submitted to stress. Recent evidence suggests that antidepressants may have antioxidant properties. However, the therapeutic potential of antioxidants as antidepressant drugs has not been systematically investigated. Therefore, this study tested the hypothesis that N-acetyl-L-cysteine (NAC), a cysteine prodrug with powerful antioxidant activity, would possess antidepressant-like properties in the forced swimming test. Male Wistar rats were subjected to 15 min of forced swimming and immediately afterward, 5, and 23 h later received intraperitoneal injections of NAC (5, 15, 50, 150, and 250 mg/kg), imipramine, (15 mg/kg) or vehicle. One hour later they were submitted to the 5 min test swimming session, where immobility time was recorded. Independent groups of animals received the same treatments and their exploratory activity was measured in an open arena for 5 min. NAC (at the doses of 15, 50, and 150 mg/kg) and imipramine induced a significant decrease in immobility time without changing exploratory behavior measured in an open arena. These results suggest that antioxidants such as NAC may have antidepressant effects.
据报道，抑郁症患者以及遭受应激的动物存在氧化应激紊乱。最近有证据表明，抗抑郁药可能具有抗氧化特性。然而，抗氧化剂作为抗抑郁药物的治疗潜力尚未得到系统研究。因此，本研究检验了以下假设：N-乙酰-L-半胱氨酸（NAC），一种具有强大抗氧化活性的半胱氨酸前体药物，在强迫游泳试验中具有类似抗抑郁的特性。将雄性Wistar大鼠进行15分钟的强迫游泳，之后立即、5小时和23小时后分别腹腔注射NAC（5、15、50、150和250mg/kg）、丙咪嗪（15mg/kg）或赋形剂。1小时后，让它们进行5分钟的试验性游泳，记录不动时间。独立的动物组接受相同的处理，并在开放场地中测量它们5分钟的探索活动。NAC（15、50和150mg/kg剂量）和丙咪嗪可显著减少不动时间，而不改变在开放场地中测量的探索行为。这些结果表明，像NAC这样的抗氧化剂可能具有抗抑郁作用。
