Effect of repeated treatment with tianeptine and fluoxetine on the centralalpha(1)-adrenergic system

Tianeptine (TIA) is an antidepressant drug which enhances the reuptake of s erotonin but, in contrast to tricyclics, shows no affinity for neurotransmi tter receptors. The present study was aimed at determining whether repeated TIA treatment induced adaptive changes in the alpha (1)-adrenergic system, similar to those reported by us earlier for tricyclic antidepressants. The experiments were carried out on male mice and rats. TIA was administered a t a dose of 5 or 10 mg/kg once or repeatedly (twice daily for 14 days) and fluoxetine (FLU), used as a reference compound, at a dose of 10 mg/kg. The obtained results showed that TIA administered repeatedly potentiated the me thoxamine- and phenylephrine (PHEN)-induced exploratory hyperactivity in ra ts and clonidine -induced aggressiveness in mice, the effects mediated by a lpha (1)-adrenoceptors. TIA given repeatedly (but not acutely) increased th e binding (B-max) of alpha (1)-adrenergic receptors in cerebral cortex for [H-3]prazosin. However, the ability of the alpha (1)-adrenoceptor agonist P HEN to compete for these sites was not significantly changed. The above res ults indicate that repeated TIA administration increases the responsiveness of the alpha (1)-adrenergic system (behavioural and biochemical changes). On the other hand, FLU did not affect any behavioural and biochemical chang es in this system. (C) 2001 Elsevier Science Ltd. All rights reserved.