Desole M S, Miele M, Esposito G, Enrico P, De Natale G, Miele E
Institute of Pharmacology, University of Sassari, Italy.
Pharmacol Res. 1991 Apr;23(3):295-306. doi: 10.1016/s1043-6618(05)80089-1.
Ascorbic acid (AA) levels and dehydroascorbic acid/ascorbic acid (DHAA/AA) ratios were determined in hypothalamus, striatum, and remaining brain of male Wistar rats, after single or repeated injections of d-amphetamine (1.8 mg/kg/day s.c.), apomorphine (1.0 mg/kg/day s.c.), and/or haloperidol (0.1 mg/kg/day i.p.). Major changes were observed in hypothalamus, in which all drugs significantly increased DHAA/AA ratio. Apomorphine and haloperidol consistently decreased AA level as well. The DHAA/AA ratio increase was observed also when apomorphine and d-amphetamine were associated with haloperidol. In striatum, apomorphine (single) and d-amphetamine (repeated) injections increased DHAA/AA ratios; such AA oxidation increase was inhibited by haloperidol; the increases (d-amphetamine) or decrease (apomorphine) of AA levels were also inhibited by haloperidol; haloperidol alone did not modify DHAA/AA ratio and induced minor changes of striatal AA level. In remaining brain, apomorphine (single) and d-amphetamine (repeated) treatment increased DHAA/AA ratio; such increase was observed also when haloperidol was associated with apomorphine or d-amphetamine; moreover, haloperidol by itself increased AA oxidation, although to a lesser extent than it did in hypothalamus. It is concluded that AA catabolism can be activated in the rat striatum by a dopaminergic mechanism; in hypothalamus and in remaining brain, the AA catabolism activation appears rather to be a non-specific effect of the pharmacological manipulation.
在雄性Wistar大鼠单次或重复注射d-苯丙胺（1.8毫克/千克/天，皮下注射）、阿扑吗啡（1.0毫克/千克/天，皮下注射）和/或氟哌啶醇（0.1毫克/千克/天，腹腔注射）后，测定其下丘脑、纹状体和其余脑组织中的抗坏血酸（AA）水平以及脱氢抗坏血酸/抗坏血酸（DHAA/AA）比值。在下丘脑中观察到主要变化，所有药物均显著提高了DHAA/AA比值。阿扑吗啡和氟哌啶醇也持续降低了AA水平。当阿扑吗啡和d-苯丙胺与氟哌啶醇联合使用时，也观察到DHAA/AA比值升高。在纹状体中，阿扑吗啡（单次）和d-苯丙胺（重复）注射提高了DHAA/AA比值；氟哌啶醇抑制了这种AA氧化增加；氟哌啶醇也抑制了AA水平的升高（d-苯丙胺）或降低（阿扑吗啡）；单独使用氟哌啶醇未改变DHAA/AA比值，并引起纹状体AA水平的轻微变化。在其余脑组织中，阿扑吗啡（单次）和d-苯丙胺（重复）处理提高了DHAA/AA比值；当氟哌啶醇与阿扑吗啡或d-苯丙胺联合使用时也观察到这种升高；此外，氟哌啶醇本身增加了AA氧化，尽管程度低于在下丘脑中的作用。结论是，AA分解代谢可通过多巴胺能机制在大鼠纹状体中被激活；在下丘脑和其余脑组织中，AA分解代谢的激活似乎是药物操作的非特异性效应。
