title: Chronic interferon-α decreases dopamine 2 receptor binding and striatal dopamine release in association with anhedonia-like behavior in nonhuman primates.
abstract: Neuroimaging studies in humans have demonstrated that inflammatory cytokines target basal ganglia function and presynaptic dopamine (DA), leading to symptoms of depression. Cytokine-treated nonhuman primates also exhibit evidence of altered DA metabolism in association with depressive-like behaviors. To further examine cytokine effects on striatal DA function, eight rhesus monkeys (four male, four female) were administered interferon (IFN)-α (20 MIU/m(2) s.c.) or saline for 4 weeks. In vivo microdialysis was used to investigate IFN-α effects on DA release in the striatum. In addition, positron emission tomography (PET) with [(11)C]raclopride was used to examine IFN-α-induced changes in DA2 receptor (D2R) binding potential before and after intravenous amphetamine administration. DA transporter binding was measured by PET using [(18)F]2β-carbomethoxy-3β-(4-chlorophenyl)-8-(2-fluoroethyl)nortropane. Anhedonia-like behavior (sucrose consumption) was assessed during saline and IFN-α administration. In vivo microdialysis demonstrated decreased release of DA after 4 weeks of IFN-α administration compared with saline. PET neuroimaging also revealed decreased DA release after 4 weeks of IFN-α as evidenced by reduced displacement of [(11)C]raclopride following amphetamine administration. In addition, 4 weeks of IFN-α was associated with decreased D2R binding but no change in the DA transporter. Sucrose consumption was reduced during IFN-α administration and was correlated with decreased DA release at 4 weeks as measured by in vivo microdialysis. Taken together, these findings indicate that chronic peripheral IFN-α exposure reduces striatal DA release in association with anhedonia-like behavior in nonhuman primates. Future studies examining the mechanisms of cytokine effects on DA release and potential therapeutic strategies to reverse these changes are warranted.
authors: 1] Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA [2] The Winship Cancer Institute, Emory University, Atlanta, GA, USA.
authors: Jennifer C
authors: JC
authors: Felger
authors: Jiyoung
authors: J
authors: Mun
authors: Heather L
authors: HL
authors: Kimmel
authors: Jonathon A
authors: JA
authors: Nye
authors: Daniel F
authors: DF
authors: Drake
authors: Carla R
authors: CR
authors: Hernandez
authors: Amanda A
authors: AA
authors: Freeman
authors: David B
authors: DB
authors: Rye
authors: Mark M
authors: MM
authors: Goodman
authors: Leonard L
authors: LL
authors: Howell
authors: Andrew H
authors: AH
authors: Miller
mesh_terms: D000661:Amphetamine / Q000494:pharmacology; D059445:Anhedonia / Q000187:drug effects*; D000818:Animals; D002250:Carbon Radioisotopes; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D018492:Dopamine Antagonists; D005260:Female; D005462:Fluorine Radioisotopes; D059907:Functional Neuroimaging; D016898:Interferon-alpha / Q000494:pharmacology*; D008253:Macaca mulatta; D008297:Male; D009662:Nortropanes; D020891:Raclopride; D011869:Radioligand Assay; D011877:Radionuclide Imaging; D017448:Receptors, Dopamine D2 / Q000378:metabolism*
chemical_list: C103655:2-carbomethoxy-3-(4-chlorophenyl)-8-(3-fluoropropyl)nortropane; D002250:Carbon Radioisotopes; D018492:Dopamine Antagonists; D005462:Fluorine Radioisotopes; D016898:Interferon-alpha; D009662:Nortropanes; D017448:Receptors, Dopamine D2; D020891:Raclopride; D000661:Amphetamine; D004298:Dopamine
references: Front Psychiatry. 2011 May 09;2:23
references: 21629844
references: Biol Psychiatry. 2011 Jul 15;70(2):175-82
references: 21277567
references: Biol Psychol. 2005 Apr;69(1):67-84
references: 15740826
references: J Neurochem. 2002 Jan;80(1):168-77
references: 11796755
references: Nature. 2013 Jan 24;493(7433):537-541
references: 23235822
references: Brain Res Brain Res Rev. 1997 Dec;25(3):312-34
references: 9495561
references: Biol Psychiatry. 2010 Oct 15;68(8):748-54
references: 20719303
references: Biol Psychiatry. 2008 Jun 1;63(11):1022-9
references: 18242584
references: Neurotox Res. 2008 Oct;14(2-3):169-83
references: 19073424
references: Eur Neuropsychopharmacol. 2013 Feb;23(2):133-45
references: 22612991
references: J Cereb Blood Flow Metab. 1994 Sep;14(5):783-801
references: 8063874
references: Nature. 2013 Jan 24;493(7433):532-6
references: 23235832
references: J Neural Transm. 1976;39(1-2):1-19
references: 1086343
references: Neuroimage. 1996 Dec;4(3 Pt 1):153-8
references: 9345505
references: Brain Behav Immun. 2013 Jul;31:153-60
references: 23072726
references: Am J Physiol Gastrointest Liver Physiol. 2004 Mar;286(3):G508-14
references: 14563668
references: J Neurosci. 2012 Jun 27;32(26):9023-34
references: 22745501
references: Curr Drug Metab. 2008 Sep;9(7):622-7
references: 18781914
references: Front Neuroendocrinol. 2012 Aug;33(3):315-27
references: 23000204
references: Biol Psychiatry. 2009 Feb 15;65(4):296-303
references: 18801471
references: Brain Behav Immun. 2013 Jul;31:161-71
references: 23064081
references: Brain Behav Immun. 2008 Aug;22(6):870-80
references: 18258414
references: N Engl J Med. 2001 Mar 29;344(13):961-6
references: 11274622
references: Mol Neurobiol. 2009 Apr;39(2):149-70
references: 19259829
references: Ann Med. 2003;35(1):2-11
references: 12693607
references: Clin Neurosci Res. 2006 Aug;6(1-2):52-68
references: 18079991
references: Arch Gen Psychiatry. 2007 Mar;64(3):327-37
references: 17339521
references: Neuropsychopharmacology. 2012 May;37(6):1422-32
references: 22257897
references: Adv Neurol. 2003;91:9-18
references: 12442660
references: Fed Proc. 1985 Jan;44(1 Pt 2):249-53
references: 3871411
references: Psychol Med. 2012 Apr;42(4):671-81
references: 21910935
references: Biol Psychiatry. 2005 Aug 1;58(3):190-6
references: 16084839
references: Nucl Med Biol. 2000 Jan;27(1):1-12
references: 10755640
references: Psychopharmacology (Berl). 1991;104(2):255-9
references: 1876670
references: Arch Gen Psychiatry. 2012 Oct;69(10):1044-53
references: 23026954
references: J Comp Physiol Psychol. 1972 Jul;80(1):11-8
references: 4625526
references: Biol Psychiatry. 2009 Feb 15;65(4):344-8
references: 18801474
references: Mol Psychiatry. 2009 May;14(5):511-22
references: 18195714
references: Neuropsychopharmacology. 2002 May;26(5):643-52
references: 11927189
references: Neuropsychopharmacology. 2007 Nov;32(11):2384-92
references: 17327884
references: Neuropsychopharmacology. 2012 Jul;37(8):1816-24
references: 22434223
references: Biol Mood Anxiety Disord. 2011 Dec 08;1(1):11
references: 22737995
references: Mol Psychiatry. 2009 Dec;14(12):1095-104
references: 18458677
references: Psychopharmacology (Berl). 2000 Feb;148(3):299-306
references: 10755743
references: Biol Psychiatry. 2007 Dec 1;62(11):1324-33
references: 17678633