El Ganouni S, Hanoun N, Boni C, Tazi A, Hakkou F, Hamon M
Department of Biology, Faculty of Sciences and Techniques, P.O. Box 577, Route de Casablanca, Settat 2000, Morocco.
Pharmacol Biochem Behav. 2004 Oct;79(2):269-77. doi: 10.1016/j.pbb.2004.07.007.
Our studies aimed at investigating whether the dihydropyridine calcium antagonist, nifedipine, could prevent anxiogenic-like consequences of diazepam withdrawal in rats. Animals withdrawn from chronic diazepam (2 mg/kg/day i.p. for 2 weeks) drank significantly less water than did control rats in the unfamiliar arm of a Y maze. This anxiogenic-like effect could be prevented by acute administration of nifedipine (at 10 mg/kg i.p., but not at lower doses), which, on its own, did not change water intake in naive rats. Given chronically in combination with diazepam for the second half of a 2-week treatment with this drug, nifedipine (at the daily dose of 5 mg/kg i.p.) also suppressed the reduction of water intake normally observed on diazepam withdrawal. Biochemical measurements showed that acutely, as well as chronically, administered nifedipine increased 5-HT turnover in the hippocampus of diazepam-treated rats, thereby suggesting that the prevention of diazepam withdrawal-induced anxiogenic behaviour by the calcium antagonist might be underlain by serotoninergic mechanisms.
我们的研究旨在调查二氢吡啶类钙拮抗剂硝苯地平是否能够预防大鼠地西泮戒断所致的焦虑样后果。从慢性给予地西泮（2毫克/千克/天，腹腔注射，持续2周）中撤药的动物，在Y迷宫的陌生臂中饮水量明显少于对照大鼠。硝苯地平急性给药（10毫克/千克，腹腔注射，但低剂量时无效）可预防这种焦虑样效应，其本身并不会改变未用药大鼠的饮水量。在为期2周的后半程治疗中，硝苯地平（5毫克/千克/天，腹腔注射）与地西泮联合长期给药，也可抑制地西泮撤药时通常观察到的饮水量减少。生化检测表明，急性及长期给药的硝苯地平均可增加地西泮处理大鼠海马中的5-羟色胺周转率，从而提示钙拮抗剂预防地西泮撤药所致焦虑行为可能是由血清素能机制介导的。
