Effect of tabernanthine on the turnover time of brain catecholamines in normal and hypobaric hypoxic rats.

The central effects of tabernanthine on noradrenaline and dopamine turnover times were studied in the hypothalamus, the striatum and the remainder of the brain of normal and hypobaric hypoxic rats, the latter state corresponding to 5,200m (410mm Hg) and 7,000m (320mm Hg). Catecholamine cerebral level were not modified by the drug in either instance. At normal atmospheric pressure the catecholamine turnover times were slightly decreased by tabernanthine. Hypobaric hypoxia alone increased noradrenaline and dopamine turnover times by inhibiting oxygen-dependent enzymes. Tabernanthine antagonized the effect of hypobaric hypoxia especially in dopaminergic areas. Antagonism was complete at 5,200m but only partial at 7,000m. This phenomenon may be related to the stimulatory properties of the drug.

Evidence for an antagonistic action of tabernanthine on hypoxia-induced changes in brain serotonin levels.

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.

The effect of various stimulated altitudes on the turnover of norepinephrine and dopamine in the central nervous system of rats.

The elimination rate constant, half-life and turnover time of dopamine (DA) and norepinephrine (NE) were determined, after inhibiting their biosynthesis by alpha-methyl-para-tyrosine (alpha MT), in the hypothalamus, striatum and the remainder of the brain of rats exposed to different degrees of hypobaric hypoxia, corresponding to altitudes of 1,800, 3,800, 5,200 and 7,000 meters. The effects varied as a function of the degree of hypoxia and the brain region studied. The turnover time of NE in the hypothalamus remained unchanged, regardless of the altitude, while in the rest of the brain the rate constant of neurotransmitter elimination decreased inversely as a linear function of the degree of hypoxia. On the contrary, the changes of the DA turnover time in the striatum and the rest of the brain, were biphasic, being accelerated by moderate altitudes (1,800 m) and retarded by the two highest simulated altitudes studied as a function of hypoxia. The differential effects of hypoxia on NE and DA turnovers are attributed to different sensitivities of the respective enzyme systems.

Evidence for an activating effect of tabernanthine on rat brain catecholamine synthesis and elimination.

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.

Changes in brain 5-hydroxytryptamine metabolism induced by hypobaric hypoxia.

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.