Decreased immobility in swimming test by homologous interferon-alpha in mice accompanied with increased cerebral tryptophan level and serotonin turnover

Neurosci Lett. 2009 Mar 13;452(2):96-100. doi: 10.1016/j.neulet.2009.01.050. Epub 2009 Jan 24.

Abstract

Animal models are used to decipher the pathophysiology of IFN-alpha-induced psychiatric complications in humans. However, the behavioral effects of IFN-alpha in rodents remain highly controversial. In contrast to homologous IFN-alpha, our recent study revealed that human IFN-alpha, which was used in many previous investigations, had no biological activity in mice. To evaluate the behavioral effects of homologous IFN-alpha in mice, adult C57BL/6J mice were treated with carrier-free murine IFN-alpha and tested on a number of behavioral paradigms. Surprisingly, contrary to previous reports, IFN-alpha treatment decreased the time spent immobile in the forced-swimming test after a single intraperitoneal injection at 2 x 10(6)IU/kg, whereas general locomotor activity was not altered. The elevated plus-maze (EPM) test showed a trend toward an increased anxiety profile in IFN-alpha-treated mice. The tail-suspension and light dark exploration test revealed no difference between IFN-alpha-treated and control animals. Interestingly, neurochemical analysis revealed significantly increased concentrations of tryptophan and 5-hydroxyindoleacetic acid (5-HIAA)/serotonin (5-HT) ratios following IFN-alpha treatment in selected brain regions. Thus, systemic murine IFN-alpha treatment increases swimming time in mice. Increased cerebral serotonin turnover as well as increased tryptophan concentrations, induced by IFN-alpha, implicates serotonergic neurotransmission in behavioral dysfunction caused by this innate immune mediator.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Anxiety / chemically induced
  • Anxiety / immunology
  • Anxiety / physiopathology
  • Anxiety Disorders / chemically induced*
  • Anxiety Disorders / immunology
  • Anxiety Disorders / physiopathology
  • Brain / drug effects*
  • Brain / immunology
  • Brain / metabolism
  • Brain Chemistry / drug effects
  • Brain Chemistry / immunology
  • Down-Regulation / drug effects
  • Down-Regulation / immunology
  • Exploratory Behavior / drug effects
  • Exploratory Behavior / physiology
  • Illness Behavior / drug effects*
  • Illness Behavior / physiology
  • Interferon-alpha / pharmacology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Motor Activity / drug effects
  • Motor Activity / immunology
  • Movement / drug effects
  • Movement / physiology
  • Neuropsychological Tests
  • Serotonin / metabolism*
  • Tryptophan / metabolism*

Substances

  • Interferon-alpha
  • Serotonin
  • Tryptophan