Effect of repeated treatment with mirtazapine on the central alpha1-adrenergic receptors

Mirtazapine (MIR)is an antidepressant which enhances noradrenergic and serotonergic 5-HT1A neurotransmission via antagomism of central alpha2 - adrenergic autoreceptors and heteroreceptors.The drugs does not inhibit noradrenaline and serotonin reuptake but blocks the 5-HT2 and 5-HT3 receptors and has high affinity only for central and peripheral histamine H1 receptors.The present study was aimed at determining whether repeated MIR treatment induced adaptive changes in the alpha1 - adrenergic receptors,similar to those reported by us early for tricyclic antidepressants,The experiments were carried out on male mice and rats.MIR was administered at a dose of 10 mg/kg once or repeatedly (twice daily for 14 days).The obtained results showed that MIR administrated repeatedly potentiated the methoxamine-induced exploratory hyperactivity in rats and clonidine- induced aggressiveness in mice,those effects being mediated by alpha1 - adrenergic receptors. MIR given repeatedly (but not acutely)increased the binding (Bmax )of [3H ]prazosin to alpha1 - adrenergic receptors in cerebral cortex,however,the ability of the alpha1 - adrenoceptor agonist phenylephrine to compete for the these sites was not significantly changed.The above results indicate that repeated MIR administration increases the responsiveness of alpha1 - adrenergic system (behavioural and biochemical changes),as tricyclics do.However, the question whether the increased functional responsiveness found in the present study is important for the clinical antidepressant efficacy,remains open.