ABSTRACT
Tabernanthine increased the synthesis and elimination of catecholamines (CA) in the striatum and the rest of the brain, but not in the hypothalamus. These data provide evidence that tabernanthine may activate CA turnover of some brain structures by acting at 2 steps of the metabolic pathway. The results are discussed in relation to a central stimulating action and a hypoxia antagonistic effect of this drug.
Subject(s)
Alkaloids/pharmacology , Brain/metabolism , Dopamine/metabolism , Ibogaine/pharmacology , Norepinephrine/metabolism , Animals , Brain/drug effects , Corpus Striatum/metabolism , Dihydroxyphenylalanine/biosynthesis , Hypothalamus/metabolism , Male , Rats , Rats, Inbred StrainsABSTRACT
The effects of tabernanthine on serotonin (5-HT) levels were determined in several brain areas of rats exposed to various simulated altitudes (1800, 5200, 7000 m). The 5-HT synthesis inhibitor, para-chlorophenylalanine (PCPA), was used to dissociate the effects occurring at synthesis and release levels. Tabernanthine antagonized the decrease in hypothalamic 5-HT levels induced by a 7000 m hypoxia and also suppressed the decrease in PCPA-induced depletion observed at 5200 and 7000 m in the hypothalamus, the striatum and the rest of the brain. It was assumed that tabernanthine stimulates different steps of 5-HT metabolism. These effects, revealed by hypoxia, are related to other peripheral and central properties of this drug.
Subject(s)
Alkaloids/pharmacology , Brain/metabolism , Hypoxia/metabolism , Ibogaine/pharmacology , Serotonin/metabolism , Altitude , Animals , Corpus Striatum/metabolism , Fenclonine/pharmacology , Hypothalamus/metabolism , Male , Rats , Rats, Inbred StrainsABSTRACT
1. 5-hydroxytryptamine (5-HT) level was measured in hypothalamus, striatum and the rest of the brain of rats exposed to 1800, 5200 and 7000 m simulated altitudes. 2. Moderate hypobaric hypoxia failed to modify 5-HT level, whereas severe hypoxia reduced the amine level by about 30%. 3. Treatment with a synthesis blocking agent (PCPA) revealed a dual effect of hypoxia on the 5-HT elimination. Increased elimination observed at 1800 m was attributed to the hypoxia-induced stress and the decrease (at 5200 and 7000 m) indicated the predominance of enzymatic inhibition. 4. It was assumed that tryptophan hydroxylase was more sensitive than monoamine oxidase to a high hypobaric hypoxia.
