Administration of pegylated interferon-α-2a or -2b does not induce sickness behavior in Lewis rats

Jennifer Loftis, Jennifer M. Wall, Rebecca L. Pagel, Peter Hauser

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Repeated administration of interferon-α (IFN-α) or pegylated IFN-α to patients with chronic hepatitis C viral infection induces a flu-like syndrome as well as neuropsychiatric side effects, which are well recognized, but poorly understood. Although pegylation appears to have improved viral response rates in patients with hepatitis C, there are still neurotoxicities associated with pegylated IFN-α therapy, in particular, depression, which can compromise and sometime prevent successful completion of antiviral treatment. This study assessed the effects of two forms of pegylated IFN-α [peginterferon-alfa-2a (PEG-2a) and peginterferon-alfa-2b (PEG-2b)] in rats in order to develop an animal model of IFN-induced "depression" (often described as sickness behavior) that can be used to more comprehensively investigate the neurochemical mechanisms of IFN-induced depression. Sixty male and female Lewis rats were randomly assigned to one of six treatment groups: (1) saline (SAL)+SAL (2) SAL+PEG-2a; (3) SAL+PEG-2b; (4) selective serotonin reuptake inhibitor (SSRI)+SAL, (5) SSRI+PEG-2a; (6) SSRI+PEG-2b. Rats were pretreated with intraperitoneal (i.p.) saline (0.9%) or 7.5 mg/kg/day fluoxetine for 1 week, followed by 3 weeks of concurrent i.p. administration of 650 μg/wk of PEG-2a or PEG-2b. Using locomotor activity, the forced swim test, and weight gain as behavioral measures of sickness behavior, our data showed that Lewis rats did not develop an IFN-induced "depressive syndrome." Western blot analyses of brain and liver tissue indicated that signal transducer and activator of transcripton (STAT1) was not phosphorylated following IFN-α administration, suggesting that the pegylated compounds may not have bound type I IFN receptors in the rat. Collectively, our data suggest that Lewis rats are likely not a useful model to study IFN-induced depression.

Original languageEnglish (US)
Pages (from-to)1289-1294
Number of pages6
JournalPsychoneuroendocrinology
Volume31
Issue number10
DOIs
StatePublished - Nov 2006

Fingerprint

Illness Behavior
Interferons
Serotonin Uptake Inhibitors
Depression
Fluoxetine
Chronic Hepatitis C
Virus Diseases
Locomotion
Depressive Disorder
Hepatitis C
Transducers
Weight Gain
Antiviral Agents
Therapeutics
Animal Models
Western Blotting
peginterferon alfa-2a
peginterferon alfa-2b
Liver
Brain

Keywords

  • Depression
  • Forced swim test
  • Pegylated interferon
  • Serotonin
  • Sickness behavior

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism
  • Psychiatry and Mental health
  • Biological Psychiatry
  • Endocrine and Autonomic Systems
  • Psychology(all)

Cite this

Administration of pegylated interferon-α-2a or -2b does not induce sickness behavior in Lewis rats. / Loftis, Jennifer; Wall, Jennifer M.; Pagel, Rebecca L.; Hauser, Peter.

In: Psychoneuroendocrinology, Vol. 31, No. 10, 11.2006, p. 1289-1294.

Research output: Contribution to journalArticle

Loftis, Jennifer ; Wall, Jennifer M. ; Pagel, Rebecca L. ; Hauser, Peter. / Administration of pegylated interferon-α-2a or -2b does not induce sickness behavior in Lewis rats. In: Psychoneuroendocrinology. 2006 ; Vol. 31, No. 10. pp. 1289-1294.
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