マウスの自発運動に及ぼすカフェインの影響

抄録

Caffeine was examined for influence upon the spontaneous motor activity in isolatedmice in relation to its doping effect by means of an electronic activity level counter(Natsume Seisakusho Co., Ltd.)") (Fig. l).The subjects used had been chosen at randoxn from among 8-week-old male miceweighing 20 to 31 g (80% variance of body weight; this range was estimated from anexperiment with 724 male mice.) of a closed colony of the ddY-F strain. Individual micewere used twice, or at 8 and 9 weeks of age, as control and test animals, respectively.Based upon the LD in isolated mice estimated prior to the experiment, caffeine50was given subcutaneously at single doses of l mg/kg (l /256 of LD..), 2, 4, 8, 16, 32, 64, 129, and l93mg/kg (3/4 of LD, .) in the form of caffeine and sodium benzoate whichcontained 9.48 or 9.90% of caffeine. Solutions of the same concentrations of sodiumbenzoate as those of the drug solutions served as controls.Measurements were made on five isolated mice for each dose. The spontaneousmotor activity was recorded for 30 minutes after a mouse had been first placed in themeasure cage without lll} treatment. Subsequently, the mouse was replaced in this cageafter having been removed for subcutaneous injection with the control or test drug.Then the spontaneous motor activity was recorded for 3 luours (room temperature:23.2+l.OC; humidity: 46.0-Hl0.4%). Behavior was also observed during the period ofrecording. The results obtained are summarized as follows.l. The LD.. of caffeine in isolated mice (8 weeks of age) calculated by Finneysgraphic approximate methods) was 257 mg/l<g by the subcutaneous route, and its 95%confidence lirait ranged from 247 to 267 mg/kg (Fig. 3).2. An appreciable increase occurred in spontaneous motor activity at as srnall adose as l mg/kg and a peak activity appeared within l hour after administration witha dose of over 2 mg/kg of caffeine. There was a progressive increase in spontaneous motoractivity with arz irncrease in dose of caffeine up to 16 mg/kg. The highest activity These results lend a positive pharmacological support to the marked doping effectof caffeine5). Furthermore, it was demonstrated that the "load cell for the strain gaugesystem" was useful for finding out qualitative changes in the spontaneous motility.