The relationship between plasma and brain caffeine and metabolite concentrations and behavioural stimulation was investigated over a 4 h time course. 2. CD-1 mice receiving single intraperitoneal doses of caffeine-sodium benzoate solution (caffeine doses: 0, 20, and 40 mg kg-1) were evaluated in an activity monitor, and their plasma and brain caffeine and metabolite concentrations were determined by high performance liquid chromatography (h.p.l.c.). 3. Kinetic variables for caffeine at low and high caffeine doses were: volume of distribution (Vd), 1.16 and 0.88 l kg-1; plasma elimination half-life (t1/2), 1.25 and 1.62 h; brain t1/2, 0.93 and 1.30 h; clearance, 0.64 and 0.38 l h-1 kg-1, respectively, with Vd and brain t1/2 differing significantly between the two caffeine doses. 4. Low-dose caffeine stimulated vertical behaviours significantly more than high-dose, during the first 150 min post-dosage; both doses stimulated vertical behaviours significantly more than vehicle treatment. 5. Low-dose and high-dose caffeine stimulated horizontal and stereotypic behaviours equivalently, during the first 150 min post-dosage; both doses stimulated these behaviours significantly more than vehicle. 6. Only later, 150 min post-dosage, did high-dose caffeine stimulate all behaviours significantly more than both low-dose and vehicle treatment; this occurred when caffeine concentrations had fallen to approximately 10 micrograms g-1 in the high-dose group. 7. The maximal stimulant effects of caffeine occurred in an intermediate concentration range, between 10-20 micrograms g-1, while lower and higher concentrations produced either no additional stimulation or decrements in activity.
摘要
在4小时的时间进程中，研究了血浆和脑内咖啡因及其代谢物浓度与行为刺激之间的关系。2. 给CD-1小鼠腹腔注射单剂量的咖啡因苯甲酸钠溶液（咖啡因剂量：0、20和40 mg kg-1），并在活动监测仪中进行评估，同时通过高效液相色谱法（h.p.l.c.）测定其血浆和脑内咖啡因及其代谢物的浓度。3. 低剂量和高剂量咖啡因的动力学变量分别为：分布容积（Vd），1.16和0.88 l kg-1；血浆消除半衰期（t1/2），1.25和1.62小时；脑内t1/2，0.93和1.30小时；清除率，0.64和0.38 l h-1 kg-1，两种咖啡因剂量之间的Vd和脑内t1/2存在显著差异。4. 在给药后的前150分钟内，低剂量咖啡因比高剂量咖啡因更显著地刺激垂直行为；两种剂量的咖啡因刺激垂直行为均显著多于溶剂处理组。5. 在给药后的前150分钟内，低剂量和高剂量咖啡因对水平行为和刻板行为的刺激作用相当；两种剂量的咖啡因刺激这些行为均显著多于溶剂处理组。6. 仅在给药后150分钟，高剂量咖啡因才比低剂量和溶剂处理组更显著地刺激所有行为；此时高剂量组中的咖啡因浓度已降至约10微克 g-1。7. 咖啡因的最大刺激作用出现在10 - 20微克 g-1的中间浓度范围内，而较低和较高浓度则不会产生额外刺激或导致活动减少。
