Effects of 5,6‐dihydroxytryptamine on Monoaminergic Neurones in the Central Nervous System of the Rat

Abstract

—The injection of 50 μg 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 μg 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 [3H]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.

Uptake Processes for Biogenic Amines

“…Several indole amines have been tested (Baumgarten et al, 1972;Horn etal., 1973;Horn, 1973b). Acetylation of the terminal amino group of 5-HT or methylation of the hydroxyl group resulted in compounds having greatly reduced affinity for the uptake sites.…”

Veratramine-induced behavior associated with serotonergic hyperfunction in mice.

“…On the contrary, Baumgarten et al confirmed that the influence of 5,6-DHT on noradrenergic neuron was negligible in rats (10). Also Berge et al were able to observe behaviors after injection of 5,6-DHT without pretreatment with desipramine (11).…”

“…A noradrenergic neuron protective agent was not used in this experiment (10,11). Behavioral observation was carried out either on the 2nd day after the injection of 5,6-DHT (20,ug/2,ul, unilateral injection) or on the 14th day after the double injections of 5,6-DHT (25 ,ug/2 ,ul X 2, bilateral injection).…”

Effect of 5,6-dihydroxytryptamine on the structure of nerve fibres in the chronically isolated cat ileum

“…It has been shown previously that 5,6-dihydroxy tryptamine (5,6-DHT) induces a chemical degeneration of serotoninergic terminals in the central nervous sys tem If applied by intraventricular injection (Baumgarten, 1971;Baumgarten et at., 1971Baumgarten et at., , 1972aCosta et at., 1972;Bjorklundet al, 1973]. The serotonin neurons possess a high affinity, selective uptake mechanism for serotonin and related compounds such as 5,6-DHT [Baumgarten et a!., 1972c], Serotonin was suggested to play a transmitter role in the mammalian gut [Bulbring andGershon, 1967;Furness and Costa, 1973].…”