Long-term effects on biotransformation of labelled choline in different parts of the rat brain induced by single choline injections

The long-term effects of single choline (Ch) injections on the uptake and metabolism of a tracer dose of 3H-Ch were studied in male rats. Choline was administered as a threshold infusion to obtain convulsions 10 and 4 weeks before sacrific (group 1). At a single threshold infusion of choline 4 weeks before sacrifice no convulsions were induced in 50% of the animals in a second group (group 2-) whereas convulsions were induced in the remainder of the animals in this group (group 2+). Group 3 contained control animals. One min. after administration of a tracer dose of 3H-Ch the animals were sacrificed and examined for 3H-total activity, 3H-Ch, 3H-acetylcholine (3H-ACh) and 3H-phosphorylcholine (3-H-PhCh). These activities were determined in three parts of the brain (cortex, striatum, midbrain + medulla oblongata). In the cortex a significant negative correlation between brain weight and 3H-ACh synthesis was seen in group 1. A comparison between group 2+ and group 2- indicated that induced convulsions were not critical for this effect. In the striatum there was a significant reduction in the total uptake of radioactivity in group 1 and group 2- when values were compared to the control group. Furthermore a significant positive correlation was detected between the concentration of radiolabel and 3H-ACh synthesis and a negative relationship with the level of 3H-Ch. In the midbrain preparation the synthesis of 3H-ACh was reduced in group 1 where a significant negative correlation was found between the average threshold dose of choline and both 3H-Ach and 3H-PhCh synthesis. Thus the Ch threshold doses given several weeks before testing seem to have long term effects on the uptake and utilization of a tracer dose of 3H-Ch in the cortex and striatum. The relation between the sensitivity to the choline threshold and the changes found later in the utilization of the tracer dose of Ch in the midbrain indicates that the midbrain could be involved in the initiation of the convulsions. (author)