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

The aim of this work was to analyze whether tianeptine, a 5-hydroxytryptamine (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 of 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.