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.
Department of Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Smetna 12, PL 31-343 Kraków, Poland. rogoz@if-pan.krakow.pl
Zofia
Z
Rogóz
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D018491:Dopamine Agonists / Q000494:pharmacology; D004347:Drug Interactions; D005106:Exploratory Behavior / Q000187:drug effects; D007099:Imipramine / Q000494:pharmacology*; D008297:Male; D008797:Metyrapone / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D044282:Receptor, Serotonin, 5-HT1A / Q000502:physiology; D044402:Receptor, Serotonin, 5-HT2A / Q000502:physiology; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology*; D011954:Receptors, Dopamine / Q000502:physiology*; D017448:Receptors, Dopamine D2 / Q000502:physiology; D050637:Receptors, Dopamine D3 / Q000502:physiology; D011985:Receptors, Serotonin / Q000502:physiology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
D000316:Adrenergic alpha-Agonists; D000928:Antidepressive Agents; D018491:Dopamine Agonists; D044402:Receptor, Serotonin, 5-HT2A; D018340:Receptors, Adrenergic, alpha-1; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D044282:Receptor, Serotonin, 5-HT1A; D007099:Imipramine; D008797:Metyrapone