EFFECTS OF 5,6‐DIHYDROXYTRYPTAMINE ON MONOAMINERGIC NEURONES IN THE CENTRAL NERVOUS SYSTEM OF THE RAT

—The injection of 50 μ g of 5,6‐dihydroxytryptamine (5,6‐HT) into a lateral ventricle of the rat depleted the spinal cord and various regions of the brain of indoleamines (presumably 5‐HT) and 5‐hydroxyindole acetic acid. The concentrations of 5‐HT were measured by two different methods: the formation of a fluorescent derivative with o ‐phthalaldehyde, and the native fluorescence in hydrochloric acid. When the results of both methods were compared on the pons and medulla 4 days after injecting 5,6‐HT, the loss in indoleamine appeared to be greater when o ‐phthalaldehyde was used. This suggests that the two methods may be measuring different compounds. According to both methods, the loss of 5‐HT persisted for several days after the injection of 5,6‐HT, but by 2 months 5‐HT concentrations (measured only by the native fluorescence procedure), had recovered to near‐normal values. The depletion of 5‐HT was most pronounced in regions adjacent to the ventricular system and in the spinal cord. Initially, caudate and septum were more affected on the side of the injection, and later showed some permanent atrophy. The injection of up to 50 μ g of 5,6‐HT did not lead to any significant loss of noradrenaline or dopamine from the brain, or to any reduction in the activity of the enzyme tyrosine hydroxylase. The drug was a potent inhibitor of the uptake of [ 3 H]5‐HT by brain slices, but was less effective in inhibiting catecholamine uptake systems. These observations suggest a preferential action on tryptaminergic neurones. Larger doses of 5,6‐HT caused a loss of catecholamines and tyrosine hydroxylase from the brain, and were severely toxic.