Effect of metyrapone on the fluoxetine-induced change in extracellular dopamine, serotonin and their metabolites in the rat frontal cortex.

Journal Title: Pharmacological Reports - Year 2010, Vol 62, Issue 6

Abstract

Major depression is frequently associated with the hyperactivity of the hypothalamic-pituitary-adrenocortical axis, and glucocorticoid synthesis inhibitors have been shown to exert antidepressant action. Metyrapone (an inhibitor of the enzyme 11-β-hydroxylase) has been found to be effective as an adjunctive therapy in combination with other antidepressants (ADs) in both treatment-resistant depression and animal models. To understand the mechanism of the clinical efficacy of a combination of an AD and metyrapone in treatment-resistant depression, the present study was aimed at determining the influence of fluoxetine (FLU; a selective serotonin reuptake inhibitor) and metyrapone, given separately or jointly, on the extracellular level of dopamine (DA), serotonin (5-HT) and their metabolites in rat frontal cortex of freely moving rats using microdialysis and high performance liquid chromatography (HPLC) with electrochemical detection. FLU (10 mg/kg) given alone increased the extracellular level of DA and 5-HT in the rat frontal cortex. Metyrapone (100 mg/kg) alone did not change the level of monoamines. Acombination of FLU and metyrapone produced the same change in the efflux of both DA and 5-HT as did FLU alone. However, the latter combination (FLU and metyrapone) produced significantly bigger increases in the levels of extracellullar DA metabolites (3,4-dihydroxyphenylacetic acid, homovanillic acid) and a 5-HT metabolite (5-hydroxyindoleacetic acid) than did FLU alone. The above findings suggest that - among other mechanisms - increases in the levels of extracellullar DA and 5-HT metabolites may play a role in the enhancement of FLU efficacy by metyrapone, and may be of crucial importance to the pharmacotherapy of drug-resistant depression.

Authors and Affiliations

Zofia Rogóż, Krystyna Gołembiowska

Keywords

Related Articles

Molecular assessment of the potential combination therapy of cytokines with biphalin and AZT for Friend leukemia virus infection in vitro.

Biphalin, a dimeric enkephalin analog, is under investigation as a potential, long-lasting medication of pain associated with chronic diseases, like cancer or AIDS. The role of cytokines, and splenocytes in anti-Friend l...

Analgesic and anticonvulsant activity of new derivatives of 2-substituted 4-hydroxybutanamides in mice.

Earlier in vitro studies of the compounds marked as GT27, GT28, GT29 and BM128 revealed their inhibitory action towards murine γ-aminobutyric acid (GABA) transporters (mGAT1-mGAT4). In the present paper, the pharmacologi...

Natural and synthetic acridines/acridones as antitumor agents: their biological activities and methods of synthesis.

Acridine derivatives constitute a class of compounds that are being intensively studied as potential anticancer drugs. Acridines are well-known for their high cytotoxic activity; however, their clinical application is li...

C3435T polymorphism of the ABCB1 gene: impact on genetic susceptibility to peptic ulcers.

The functional single nucleotide polymorphism (SNP) C3435T in exon 26 of the ABCB1 gene encoding the xenobiotic transporter P-glycoprotein (P-gp) may influence susceptibility to several diseases, as well as the clinical...

Download PDF file
  • EP ID EP160440
  • DOI -
  • Views 98
  • Downloads 0

How To Cite

Zofia Rogóż, Krystyna Gołembiowska (2010). Effect of metyrapone on the fluoxetine-induced change in extracellular dopamine, serotonin and their metabolites in the rat frontal cortex.. Pharmacological Reports, 62(6), 1015-1022. https://europub.co.uk/articles/-A-160440