Kaplan G B, Greenblatt D J, Leduc B W, Thompson M L, Shader R I
Department of Psychiatry, Tufts University School of Medicine, Boston.
J Pharmacol Exp Ther. 1989 Mar;248(3):1078-83.
CD-1 mice were treated with caffeine-sodium benzoate solution (caffeine doses: 0, 5, 15 or 30 mg/kg i.p.) to determine plasma and brain concentrations, effects on benzodiazepine receptor binding based on specific uptake of a high affinity ligand, and locomotor activity. There was a linear relationship between caffeine dose and mean brain or plasma concentrations, but concentrations varied considerably at any given dose. There were also linear relationships between plasma and brain concentrations of caffeine and each metabolite, with caffeine itself having the greatest brain:plasma uptake ratio. Benzodiazepine receptor binding was determined based on uptake of the benzodiazepine receptor ligand [3H]Ro15-1788, 3 microCi i.v. given 40 min after caffeine (30 mg/kg). Nonspecific binding was measured in animals pretreated with saturating doses of clonazepam. Specific uptake (measured by subtracting nonspecific from total [3H] Ro15-1788 uptake) increased significantly with caffeine as opposed to vehicle treatment in the cortex, hippocampus and hypothalamus. Brain caffeine concentrations associated with enhanced uptake were between 11 to 17 micrograms/g. Total locomotor activity and activity at 60 min, measured by an infrared sensor system, increased progressively with brain caffeine concentrations when comparing the following groups: 0, 2 to 9 micrograms/g of brain and 9 to 20 micrograms/g. Animals with brain concentrations exceeding 20 micrograms/g showed a decline in both measures but activity was significantly greater than placebo. In conclusion, brain caffeine concentrations between 9 to 20 micrograms/g are associated with increases in specific ligand uptake and motor activity.
用咖啡因 - 苯甲酸钠溶液（咖啡因剂量：0、5、15或30mg/kg腹腔注射）处理CD - 1小鼠，以测定血浆和脑内浓度、基于高亲和力配体的特异性摄取对苯二氮䓬受体结合的影响以及运动活性。咖啡因剂量与平均脑内或血浆浓度之间存在线性关系，但在任何给定剂量下浓度变化很大。咖啡因及其每种代谢物的血浆和脑内浓度之间也存在线性关系，其中咖啡因本身的脑摄取与血浆摄取之比最大。基于苯二氮䓬受体配体[3H]Ro15 - 1788的摄取来测定苯二氮䓬受体结合，在给予咖啡因（30mg/kg）40分钟后静脉注射3微居里。在预先用饱和剂量氯硝西泮处理的动物中测量非特异性结合。与溶剂处理相比，咖啡因使皮质、海马和下丘脑的特异性摄取（通过从总[3H]Ro15 - 1788摄取中减去非特异性摄取来测量）显著增加。与摄取增强相关的脑咖啡因浓度在11至17微克/克之间。当比较以下组时，通过红外传感器系统测量的总运动活性和60分钟时的活性随脑咖啡因浓度逐渐增加：0、2至9微克/克脑和9至20微克/克脑。脑浓度超过20微克/克的动物在这两项测量中均显示下降，但活性仍显著高于安慰剂。总之，脑咖啡因浓度在9至20微克/克之间与特异性配体摄取和运动活性增加有关。
