Changes in cholinergic function in rat brain late in abstinence after chronic barbital treatment

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.