Nordberg A, Wahlström G
Drug Alcohol Depend. 1981 Feb;7(1):51-61. doi: 10.1016/0376-8716(81)90117-4.
The effect of a forced long-term barbital treatment (daily dosage about 200 mg/kg for 32 weeks) on cholinergic brain mechanisms was studied on days 53 and 81 - 83 after withdrawal. Some of the barbital-treated rats were given a single injection of atropine (8 mg/kg intraperitoneally) on the third day of abstinence (group BA), while the other barbital-treated rats received saline (group BS). The sensitivity to a threshold dose of choline was tested on day 53. The rats in the BS group were more sensitive to choline than those in the control groups. When the rats were sacrificed on day 81 - 83 after withdrawal, a significant reduction in brain weight was found in group BS but not in group BA when compared with the controls. At the same time the content of endogenous acetylcholine was reduced in the barbital-treated animals and this reduction seemed to be positively related to the reduction of brain weight. After sacrifice the uptake and biotransformation of a tracer dose of radioactive choline were also studied. A marked difference was seen between the brain regions. In the cortex the biosynthesis of radioactive acetylcholine was significantly lower in the BS group than in the control group; the BA group was in between. In the midbrain no significant changes in radioactive acetylcholine synthesis were seen. In the striatum a significantly lower formation of radioactive acetylcholine was found in the BA group and a lower radioactive phosphorylcholine formation in he BS group. The studied variables indicate that prolonged barbital treatment induces changes in cholinergic function in rat brain extending considerably beyond withdrawal. Treatment with atropine early in the abstinence seemed to reduce these changes.
在停药后第53天以及第81 - 83天，研究了长期强制给予巴比妥治疗（每日剂量约200毫克/千克，持续32周）对胆碱能脑机制的影响。在戒断的第三天，一些接受巴比妥治疗的大鼠腹腔注射一次阿托品（8毫克/千克）（BA组），而其他接受巴比妥治疗的大鼠注射生理盐水（BS组）。在第53天测试了对阈剂量胆碱的敏感性。与对照组相比，BS组大鼠对胆碱更敏感。在停药后第81 - 83天处死大鼠时，与对照组相比，发现BS组脑重量显著降低，而BA组未出现这种情况。同时，接受巴比妥治疗的动物体内内源性乙酰胆碱含量降低，且这种降低似乎与脑重量的减轻呈正相关。处死大鼠后，还研究了示踪剂量放射性胆碱的摄取和生物转化。脑区之间存在明显差异。在皮质中，BS组放射性乙酰胆碱的生物合成显著低于对照组；BA组介于两者之间。在中脑，放射性乙酰胆碱合成未见显著变化。在纹状体中，BA组放射性乙酰胆碱的生成显著降低，BS组放射性磷酸胆碱的生成较低。所研究的变量表明，长期巴比妥治疗可诱导大鼠脑内胆碱能功能发生变化，且这种变化在停药后仍持续较长时间。在戒断早期用阿托品治疗似乎可减轻这些变化。
