Nowycky M C, Walters J R, Roth R H
J Neural Transm. 1978;42(2):99-116. doi: 10.1007/BF01675349.
At various time points following acute and chronic administration of morphine to rats, dopamine transmitter metabolism and neuronal activity were determined. Following acute injection of morphine (20 mg/kg intraperitoneally), dopamine cell firing rates increased slowly and steadily. This slow increase was accompanied by a similar slow increase in the accumulation of the dopamine metabolite, dihydroxyphenylacetic acid (DOPAC). Apparent in vivo tyrosine hydroxylase activity, measured by dopa accumulation following inhibition of dopa decarboxylase, also increased. In chronically treated animals the average firing rate of dopamine cells was measured two hours after the last injection of morphine. The distribution of dopamine cell firing rates was significantly higher than in controls. DOPAC levels and in vivo tyrosine hydroxylase activity were also increased at this time. When morphine (100 mg/kg intraperitoneally) was administered to chronically treated animals 12 hours after the last injection a slow increase of firing rates was observed similar to that seen in naive animals after an acute morphine injection. In chronically morphine treated animals naloxone caused a rapid dose-dependent decrease in firing rates and DOPAC levels. In vivo tyrosine hydroxylase activity was not changed.
在对大鼠急性和慢性给予吗啡后的不同时间点，测定了多巴胺递质代谢和神经元活性。急性注射吗啡（20毫克/千克腹腔注射）后，多巴胺细胞放电率缓慢而稳定地增加。这种缓慢增加伴随着多巴胺代谢物二羟基苯乙酸（DOPAC）积累的类似缓慢增加。通过抑制多巴脱羧酶后多巴积累来测量的体内酪氨酸羟化酶活性也增加。在长期治疗的动物中，在最后一次注射吗啡两小时后测量多巴胺细胞的平均放电率。多巴胺细胞放电率的分布显著高于对照组。此时DOPAC水平和体内酪氨酸羟化酶活性也增加。在最后一次注射12小时后，对长期治疗的动物腹腔注射吗啡（100毫克/千克），观察到放电率缓慢增加，类似于初次注射吗啡的未处理动物。在长期接受吗啡治疗的动物中，纳洛酮导致放电率和DOPAC水平迅速出现剂量依赖性下降。体内酪氨酸羟化酶活性未改变。
