Kayir Hakan, Uzbay I Tayfun
Faculty of Medicine, Department of Medical Pharmacology, Gülhane Military Medical Academy, Etlik 06018, Ankara, Turkey.
Psychopharmacology (Berl). 2004 Feb;172(1):11-5. doi: 10.1007/s00213-003-1625-5. Epub 2003 Nov 18.
Nitric oxide (NO) is implicated in the acute locomotor activating effects of some addictive drugs such as amphetamine and cocaine, but has not been investigated in the case of caffeine.
We investigated the effects of a nitric oxide synthase (NOS) inhibitor Nomega-Nitro- l-arginine methyl ester ( l-NAME) and a combination of l-arginine, a NO precursor, and l-NAME on caffeine induced locomotor activity in Swiss Webster mice.
Locomotor activity was recorded for 30 min immediately following caffeine (0.25-128 mg/kg) or saline administration. In a further study, l-NAME (15 and 30 mg/kg) was administered to another group of mice 30 min before caffeine (1 and 16 mg/kg) injections. Finally, l-arginine (1000 mg/kg), a nitric oxide precursor, was administered 20 min before the l-NAME (15 and 30 mg/kg) treatments and locomotor activities were again recorded immediately after caffeine (1 and 16 mg/kg) injections.
Caffeine (0.5-16 mg/kg) significantly increased locomotor activity, while l-NAME (30 mg/kg) blocked caffeine (1 and 16 mg/kg)-induced locomotor activity. The low dose of l-NAME blocked only caffeine (1 mg/kg)-induced locomotor activity. l-Arginine reversed the inhibitory effects of l-NAME on caffeine-induced locomotor activity. l-NAME and l-arginine had no effect on the locomotor activity of the mice when given by themselves.
The results suggest that caffeine-induced locomotor activity might be modulated by NO in mice.
一氧化氮(NO)与某些成瘾性药物如苯丙胺和可卡因的急性运动激活作用有关,但咖啡因的情况尚未得到研究。
我们研究了一氧化氮合酶(NOS)抑制剂Nω-硝基-L-精氨酸甲酯(L-NAME)以及NO前体L-精氨酸与L-NAME的组合对瑞士韦伯斯特小鼠咖啡因诱导的运动活动的影响。
在给予咖啡因(0.25 - 128mg/kg)或生理盐水后立即记录30分钟的运动活动。在进一步的研究中,在给另一组小鼠注射咖啡因(1和16mg/kg)前30分钟给予L-NAME(15和30mg/kg)。最后,在给予L-NAME(15和30mg/kg)处理前20分钟给予一氧化氮前体L-精氨酸(1000mg/kg),并在注射咖啡因(1和16mg/kg)后立即再次记录运动活动。
咖啡因(0.5 - 16mg/kg)显著增加运动活动,而L-NAME(30mg/kg)阻断咖啡因(1和16mg/kg)诱导的运动活动。低剂量的L-NAME仅阻断咖啡因(1mg/kg)诱导的运动活动。L-精氨酸逆转了L-NAME对咖啡因诱导的运动活动的抑制作用。L-NAME和L-精氨酸单独给予时对小鼠的运动活动没有影响。
结果表明咖啡因诱导的运动活动可能在小鼠中受到NO的调节。