TY - JOUR
T1 - Administration of pegylated interferon-α-2a or -2b does not induce sickness behavior in Lewis rats
AU - Loftis, Jennifer M.
AU - Wall, Jennifer M.
AU - Pagel, Rebecca L.
AU - Hauser, Peter
N1 - Funding Information:
The authors would like to thank Dr. S. Paul Berger for the use of his automated locomotor activity chambers and research assistants: Julia Carr and Zachary Vande Griend for their help with drug administration and behavioral testing. This work was supported in part by a grant from Hoffman-La Roche, Inc.
PY - 2006/11
Y1 - 2006/11
N2 - 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.
AB - 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.
KW - Depression
KW - Forced swim test
KW - Pegylated interferon
KW - Serotonin
KW - Sickness behavior
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U2 - 10.1016/j.psyneuen.2006.07.006
DO - 10.1016/j.psyneuen.2006.07.006
M3 - Article
C2 - 17049181
AN - SCOPUS:33751343398
SN - 0306-4530
VL - 31
SP - 1289
EP - 1294
JO - Psychoneuroendocrinology
JF - Psychoneuroendocrinology
IS - 10
ER -