title: Recombinant human interferon-alpha does not alter reward behavior, or neuroimmune and neuroendocrine activation in rats.
abstract: Recombinant human interferon-alpha (IFN-alpha) induces depression, and neuroendocrine and neuroimmune activation, in a significant number of patients undergoing treatment for viral illnesses (e.g., hepatitis C), yet these effects have not been consistently reproduced in rodents. As such, we sought to determine the effects of acute or chronic IFN-alpha treatment on basic reward and immobility in the forced swim test (FST), neuroendocrine and neuroimmune activation, and monoamine turnover in brain. In the first experiment, male Wistar rats (N = 7/group) treated with human recombinant IFN-alpha (100,000 IU/kg, i.p.), as compared to saline, did not exhibit alterations to rate of sucrose pellet self-administration or total reinforcers obtained, corticosterone release, plasma IL-6 release, IL-1beta or IL-6 mRNA expression in hippocampus, or monoamine turnover in prefrontal cortex, striatum, nucleus accumbens, or amygdala. However, acute IFN-alpha decreased body weight and produced a trend toward reduced food consumption in the home cage 2 h after injection. In the second experiment, Wistar rats (N=4/group) were subjected to a chronic treatment regimen of saline or IFN-alpha (100,000 IU/kg, i.p.) once daily for 14 consecutive days. The data reveal that animals exposed to chronic IFN-alpha exhibited similar amounts of time immobile and similar latencies to primary immobility in the FST as compared to saline-treated controls. Chronic IFN-alpha did not induce corticosterone release, plasma TNF-alpha, or IL-6 release. Tissue monoamine analysis revealed that chronic IFN-alpha reduced DA levels in prefrontal cortex, and decreased 5-HT levels and increased 5-HT turnover in amygdala. In the third experiment, Wistar rats (N = 4/group) were exposed to either acute or chronic pegylated IFN-alpha (pegIFN-alpha: 3.25, 10 or 75 mg/kg, i.p.) at one of several time points from 1 h to 23 days. The data reveal that neither acute nor chronic pegIFN-alpha induced corticosterone release. Overall, the current report demonstrates that neither acute nor chronic IFN-alpha induced depressive-like behavior and neither IFN-alpha nor peg-IFN-alpha was capable of inducing neuroendocrine or neuroimmune activation. Despite the neurochemical alterations observed in the chronic treatment regimen, the data indicate that recombinant human IFN-alpha does not produce a robust model of depressive-like behavior in rodents.
authors.affiliation: Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, 740 Westwood Boulevard, NPI A8-148, Los Angeles, CA 90024, USA. rdlagarza@mednet.ucla.edu
authors.forename: Richard
authors.initials: R
authors.lastname: De La Garza
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Asnis
authors.forename: Erika
authors.initials: E
authors.lastname: Pedrosa
authors.forename: Cordelia
authors.initials: C
authors.lastname: Stearns
authors.forename: Alexandra L
authors.initials: AL
authors.lastname: Migdal
authors.forename: John F
authors.initials: JF
authors.lastname: Reinus
authors.forename: Rajendra
authors.initials: R
authors.lastname: Paladugu
authors.forename: Sridevi
authors.initials: S
authors.lastname: Vemulapalli
mesh_terms: D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects; D003216:Conditioning, Operant / Q000187:drug effects*; D003345:Corticosterone / Q000097:blood; D015342:DNA Probes; D003866:Depressive Disorder / Q000139:chemically induced / Q000523:psychology; D006801:Humans; D007109:Immunity / Q000187:drug effects*; D007370:Interferon Type I / Q000737:chemistry / Q000494:pharmacology*; D007375:Interleukin-1 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009490:Neurosecretory Systems / Q000187:drug effects*; D011092:Polyethylene Glycols / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012201:Reward; D013550:Swimming / Q000523:psychology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D015306:Biogenic Monoamines; D015342:DNA Probes; D007370:Interferon Type I; D007375:Interleukin-1; D015850:Interleukin-6; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D011092:Polyethylene Glycols; D003345:Corticosterone