Behavioral and physiological effects of a single injection of rat interferon-alpha on male Sprague-Dawley rats: a long-term evaluation

Brain Res. 2006 Jun 20;1095(1):96-106. doi: 10.1016/j.brainres.2006.04.014. Epub 2006 May 18.


Interferon-alpha (IFN-alpha) is a cytokine used as a first line of defense against diseases such as cancer and hepatitis C. However, reports indicate that its effectiveness as a treatment is countered by central nervous system (CNS) disruptions in patients. Our work explored the possibility that it may also cause long-term behavioral disruptions by chronicling the behavioral and physiological disturbances associated with a single injection of vehicle, 10, 100, or 1,000 units of IFN-alpha in male Sprague-Dawley rats (n = 5/dose). Following 1 day of locomotor baseline collection, we monitored sickness behaviors (ptosis, piloerection, lethargy, and sleep), food and water intake, body weight, temperature, and motor activity. Observations were recorded 4 days prior to and 4 days following the IFN-alpha injection. Temperature and sickness behaviors were recorded three times daily at 9:00, 15:00, and 21:00 h, and all other indices, once daily. On the injection day, temperature values were highest in the animals receiving the 10-unit IFN-alpha dose 15 min and 13 h post-injection. In the case of sickness behaviors, a significant increase was observed in piloerection in all IFN-alpha groups at each time point measured, while the scores of the rats in the vehicle condition remained unchanged between pre- and post-injection days. Analyses of overall sickness behaviors during morning and night observation periods indicated increased scores in all IFN-alpha groups following injection. Cumulatively, these data suggest that a single IFN-alpha exposure may elicit long-term behavioral disruptions and that its consequences should be thoroughly investigated for its use in clinical populations.

Publication types

  • Comparative Study
  • Evaluation Study

MeSH terms

  • Analysis of Variance
  • Animals
  • Behavior, Animal / drug effects*
  • Body Temperature / drug effects
  • Body Weight / drug effects
  • Dose-Response Relationship, Drug
  • Drinking / drug effects
  • Immunologic Factors / administration & dosage*
  • Interferon-alpha / administration & dosage*
  • Locomotion / drug effects
  • Male
  • Motor Activity / drug effects
  • Physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Stereotyped Behavior / drug effects
  • Time Factors


  • Immunologic Factors
  • Interferon-alpha