Effect of repeated treatment with olanzapine or olanzapine plus fluoxetine on tyrosine hydroxylase in the rat locus coeruleus

The International Journal of Neuropsychopharmacology
Gregory A Ordway, Katalin Szebeni

Abstract

Repeated treatment of rats with antidepressant drugs down-regulates tyrosine hydroxylase (TH) in the locus coeruleus (LC). Using this effect as a model system, this study evaluated the antidepressant potential of the atypical antipsychotic drug, olanzapine. In an initial study, rats were treated i.p. with saline, olanzapine (3 mg/kg), or imipramine (15 mg/kg) once daily for 18 d. Three additional groups of rats received the same treatments that were overlapped with reserpine administration (0.5 mg/kg.d for 21 d). In a second study, groups of rats were treated twice daily with saline, olanzapine (5 mg/kg.d), fluoxetine (15 mg/kg.d), or fluoxetine (15 mg/kg.d) plus olanzapine (5 mg/kg.d) for 1, 6, 12 and 18 d. In the initial study, imipramine produced a 45% reduction in LC TH levels, while olanzapine had no effect. In reserpinized rats, olanzapine exhibited an action that was opposite to that of imipramine, although this effect did not reach statistical significance. In the second study, olanzapine treatment alone or in combination with fluoxetine up-regulated TH in the LC, while fluoxetine alone had no effect. When fluoxetine was co-administered, olanzapine-induced increases in LC TH were more robust and occurred earlier in the ...Continue Reading

Citations

Jun 25, 2008·European Archives of Psychiatry and Clinical Neuroscience·Tomasz GosBernhard Bogerts
Jun 24, 2006·Drug Discovery Today·Kurt Rasmussen
Jul 10, 2013·European Journal of Pharmacology·Andrea de BartolomeisCarmine Tomasetti
Oct 25, 2012·Neuroscience and Biobehavioral Reviews·Ulrich Hegerl, Tilman Hensch
Oct 28, 2008·The International Journal of Neuropsychopharmacology·Charles H K WestJay M Weiss
Apr 11, 2017·Journal of Controlled Release : Official Journal of the Controlled Release Society·Yan-Jye ShyongFeng-Huei Lin
Sep 17, 2021·Pharmacogenomics·Pablo ZubiaurFrancisco Abad-Santos

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