Effect of repeated co-treatment with imipramine and metyrapone on the behavioral reactivity of the central serotonin, dopamine and alpha 1-adrenergic systems in rats.

The aim of present study was to examine the effect of repeated co-treatment with imipramine and metyrapone on the development of adaptive changes in the function of central serotonin 5-HT1A and 5-HT2A, dopamine D2/3 and alpha 1-adrenergic receptors in rats. The obtained results showed that repeated co-treatment with imipramine (5 or 10 mg/kg) and metyrapone (50 mg/kg) (twice daily for 14 days) either induced more potent inhibition of the behavioral syndrome evoked by 5-HT1A and 5-HT2A receptor agonists (8-OH-DPAT and (+/-)DOI, respectively), or did no change the action of amphetamine and wuinpirole (a dopamine D2/3 agonist) or phenylephrine (an alpha 1-adrenergic agonist) compared to treatment with either drug alone. The results described in the present paper support the hypothesis that repeated co-treatment with imipramine and metyrapone may possess more effective antidepressant activity than the treatment with imipramine alone, and that, among other mechanisms, 5-HT1A- and 5-HT2A (but not dopamine D2/3- or alpha 1-adrenergic) receptors may also play some role in this effect.