Cellular and Molecular Neurobiology

, Volume 19, Issue 1, pp 109–117

Alterations of Tubulin Function Caused by Chronic Antidepressant Treatment in Rat Brain

  • Hiroki Kamada
  • Toshikazu Saito
  • Shinichi Hatta
  • Sadamu Toki
  • Hiroki Ozawa
  • Masayuki Watanabe
  • Naohiko Takahata
Article

Abstract

1. Antidepressants have been used clinically for many years; however, the neurochemical mechanism for their therapeutic effect has not been clarified yet. Recent reports indicate that chronic antidepressant treatment directly affects the postsynaptic membrane to increase the coupling between the stimulatory GTP-binding (G) protein, Gs, and adenylyl cyclase. Tubulin, a cytoskeletal element, is involved in the stimulatory and inhibitory regulation of adenylyl cyclase in rat cerebral cortex via direct transfer of GTP to G proteins. In this study, we investigated whether the functional change of the adenylyl cyclase system caused by chronic antidepressant treatment involves an alteration of tubulin function in the regulation of adenylyl cyclase activity.

2. Male Sprague–Dawley rats were treated once daily with amitriptyline or saline by intraperitoneal injection (10 mg/kg) for 21 days, and their cerebral cortex membranes and GppNHp-liganded tubulin (tubulin-GppNHp) were prepared for what.

3. GppNHp-stimulated adenylyl cyclase activity in cortex membranes from amitriptyline-treated rats was significantly higher than that in control membranes. Furthermore, tubulin–GppNHp prepared from amitriptyline-treated rats was more potent than that from control rats in the stimulation of adenylyl cyclase activity in the cortex membranes of the controls. However, there was no significant difference in manganese-stimulated adenylyl cyclase activity between control and amitriptyline-treated rats.

4. The present results suggest that chronic antidepressant treatment enhances not only the coupling between Gs and the catalytic subunit of adenylyl cyclase but also tubulin interaction with Gs in the cerebral cortex of the rat.

antidepressant tubulin GTP-binding protein adenylyl cyclase 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Copyright information

© Kluwer Academic/Plenum Publishers 1999

Authors and Affiliations

  • Hiroki Kamada
    • 1
  • Toshikazu Saito
    • 1
  • Shinichi Hatta
    • 2
  • Sadamu Toki
    • 1
  • Hiroki Ozawa
    • 1
  • Masayuki Watanabe
    • 1
  • Naohiko Takahata
    • 1
  1. 1.Department of Neuropsychiatry, School of MedicineSapporo Medical UniversityChuo-ku, SapporoJapan
  2. 2.Department of Pharmacology, School of MedicineSapporo Medical UniversityChuo-ku, SapporoJapan

Personalised recommendations