EFFECT OF PROLONGED ADMINISTRATION OF TIANEPTINE ON 5-HT NEUROTRANSMISSION - AN ELECTROPHYSIOLOGICAL STUDY IN THE RAT HIPPOCAMPUS AND DORSAL RAPHE

Extracellular unitary recordings of dorsal hippocampus CA(3) pyramidal neurons and of dorsal raphe 5-hydroxytryptamine (5-HT) neurons were u sed to assess the effect of tianeptine, a putative antidepressant, on the efficacy of 5-HT neurotransmission. Sustained tianeptine administr ation (20 mg/kg/day, s.c. x 14 days) did not modify the firing activit y of 5-HT neurons in the dorsal raphe. Their responsiveness to the int ravenous injection of LSD, an agonist of the somatodendritic 5-HT auto receptor, and of 8-OH-DPAT, a selective 5-HT1A agonist, was also unaff ected by this treatment. The responsiveness of CA(3) pyramidal neurons to microiontophoretic application of 5-HT remained unchanged after su stained tianeptine administration, but it was markedly enhanced in rat s treated with repeated electroconvulsive shocks. Finally, the duratio n of suppression of firing activity of CA(3) pyramidal neurons produce d by electrical stimulation of the ascending 5-HT pathway, delivered a t 1 Hz and 5 Hz, was not modified in rats treated with tianeptine. Met hiothepin, an antagonist of the terminal auto receptor enhanced the ef fectiveness of 5-HT pathway stimulation to the same extent in control and tianeptine-treated rats. The present results indicate that, admini stered at a dose known to stimulate 5-HT reuptake (20 mg/kg/ day, s.c. ; by minipump), and for a period of time (14 days) for which other ant idepressant treatments have been shown to enhance 5-HT function, tiane ptine does not modify the efficacy of 5-HT synaptic transmission in th e rat hippocampus.