Effects of tianeptine on 5-HTP- and dextrofenfluramine-induced hypophagia in the rat

doi:10.1016/0091-3057(93)90037-T

Pharmacology Biochemistry and Behavior

Volume 44, Issue 4, April 1993, Pages 989-992

https://doi.org/10.1016/0091-3057(93)90037-T Get rights and content

Abstract

The aim of this work was to analyze whether tianeptine, a 5-hydroxytrptamine (5-HT) reuptake enhancer, opposes the loss in food intake elicited by 5-HT release. Rats were food deprived for 20 h, pretreated either with saline or 7-[3-chloro-6-methyl-5, 5-dioxo-6, 11-dihydro-(c,f)-dibenzo-(1,2-thiazepine)-11-yl- amino]-heptanoic acid (tianeptine, 10 mg/kg, IP), and injected 1 h afterwards either with saline, with the 5-HT precursor L-5-hydroxytryptophan (5-HTP, 20 or 40 mg/kg, IP), or with the 5-HT reuptake inhibitor/5-HT releaser dextrofenfluramine (d-FEN, 1.5 or 3 mg/kg, IP). Diets were then presented 30 min later, and individual food intakes were measured 1, 2, 3, and 4 h after food presentation. Saline- and tianeptine-pretreated saline-injected rats ate the most, and to a similar extent, during the first hour of food presentation; however, in these animals tianeptine pretreatment tended to diminish rates of eating throughout the last 3 h analysis. Administration of 5-HTP or d-FEN triggered immediate dose-dependent decreases in food intake that were not affected by tianeptine pretreatment. In addition, tianeptine pretreatment did not alter either brain d-FEN or d-norfenfluramine levels, thereby suggesting that the lack of effect of tianeptine against d-FEN-elicited hypophagia could not be accounted for by changes in d-FEN metabolism. This study opens the possibility that tianeptine counteracts the effects of 5-HT release in some paradigms but not in others.

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Tianeptine facilitates spreading depression in well-nourished and early-malnourished adult rats
2013, European Journal of Pharmacology
Citation Excerpt :
The main pharmacological mechanism of action of tianeptine is based on its capacity to reduce serotonin levels in several brain areas (Lechin et al., 2006; Mennini et al., 1987); accordingly, an increase in body weight could be expected following treatment. However, in contrast, hypophagia has been observed in rats after tianeptine treatment (Chaouloff, 1993). Concerning nutritional status, our early-malnourished animals presented lower body weights compared to the well-nourished ones, and this weight difference persisted until adulthood when malnourishment was no longer present.
Nutritional status during development can modify the brain's electrophysiological properties and its response to drugs that reduce the serotonin availability in the synaptic cleft. Here we used cortical spreading depression (CSD) in the rat as a neurophysiological parameter to investigate the interaction between nutritional status and treatment with tianeptine, a serotonin uptake enhancer. From postnatal day 2 to 24, well-nourished and early-malnourished rat pups were s.c. injected with tianeptine (5 or 10 mg/kg; 10 ml/kg) or equivalent volume of saline solution (control group). When the animals were 25–30 days old, CSD was recorded on the brain cortical surface. In the well-nourished rats, but not in the malnourished group, systemic tianeptine dose-dependently increased the CSD propagation velocity, with 10 mg/kg producing a significant (P<0.05) effect. An experiment in adult rats showed that cortical topical application of tianeptine solutions (5 mg/ml, 10 mg/ml, and 20 mg/ml) increased the CSD propagation in both the well-nourished and early-malnourished conditions. In well-nourished animals, 0.5 mg/ml topical tianeptine did not affect CSD propagation, and 2 mg/ml produced a small, but significant CSD acceleration. Our results indicate a facilitating action of tianeptine on CSD propagation, probably via tianeptine's pharmacological action on the serotonin system. These findings support previous data suggesting an antagonistic role of the serotoninergic system on CSD.
Serotonin a la carte: Supplementation with the serotonin precursor 5-hydroxytryptophan
2006, Pharmacology and Therapeutics
This paper reviews the preclinical and clinical evidence regarding the use of the dietary supplement 5-hydroxytryptophan (5-HTP) for the treatment of depression. In the absence of supplementation with exogenous 5-HTP, the amount of endogenous 5-HTP available for serotonin synthesis depends on the availability of tryptophan and on the activity of various enzymes, especially tryptophan hydroxylase, indoleamine 2,3-dioxygenase, and tryptophan 2,3-dioxygenase (TDO). Factors affecting each of these are reviewed. The amount of 5-HTP reaching the central nervous system (CNS) is affected by the extent to which 5-HTP is converted to serotonin in the periphery. This conversion is controlled by the enzyme amino acid decarboxylase, which, in the periphery, can be blocked by peripheral decarboxylase inhibitors (PDIs) such as carbidopa. Preclinical and clinical evidence for the efficacy of 5-HTP for depression is reviewed, with emphasis on double-blind, placebo-controlled (DB-PC) trials. Safety issues with 5-HTP are also reviewed, with emphasis on eosinophilia myalgia syndrome (EMS) and serotonin syndrome.
Dexfenfluramine: An updated review of its therapeutic use in the management of obesity
1996, Drugs
Tianeptine: A Review of its Pharmacodynamic and Pharmacokinetic Properties, and Therapeutic Efficacy in Depression and Coexisting Anxiety and Depression
1995, Drugs

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Brief communicationEffects of tianeptine on 5-HTP- and dextrofenfluramine-induced hypophagia in the rat

Abstract

Neuropharmacology

Pharmacol. Biochem. Behav.

Eur. Neuropsychopharmacol.

Biol. Psychiatry

Brain Res.

Brain Res.

Neuropharmacology

Neuropharmacology

Eur. J. Pharmacol.

Neuropharmacology

The effects of tianeptine and other antidepressants on a rat model of depression

Br. J. Psychiat.

Antidepressant and anxiolytic activities of tianeptine: An overview of clinical trials

Clin. Neuropharmacol.

Brief communication
Effects of tianeptine on 5-HTP- and dextrofenfluramine-induced hypophagia in the rat