title: Levodopa reverses cytokine-induced reductions in striatal dopamine release.
abstract: BACKGROUND
  Studies using neuroimaging and in vivo microdialysis in humans and nonhuman primates indicate that inflammatory cytokines such as interferon-alpha reduce dopamine release in the ventral striatum in association with depressive symptoms including anhedonia and psychomotor slowing.
  
  
  METHODS
  Herein, we examined whether reduced striatal dopamine release in rhesus monkeys chronically treated with interferon-alpha can be restored by administration of the dopamine precursor levodopa via reverse in vivo microdialysis.
  
  
  RESULTS
  Levodopa completely reversed interferon-alpha-induced reductions in striatal dopamine release. No changes were found in the 3,4-dihydroxyphenylacetic acid to dopamine ratio, which increases when unpackaged dopamine is metabolized via monoamine oxidase.
  
  
  CONCLUSIONS
  These findings suggest that inflammatory cytokines reduce the availability of dopamine precursors without affecting end-product synthesis or vesicular packaging and/or release and provide the foundation for future studies investigating therapeutic strategies that facilitate availability of dopamine precursors to improve depressive symptoms in patient populations with increased inflammation.
authors: Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA (Drs Felger, Hernandez, and Miller); The Winship Cancer Institute, Emory University, Atlanta, GA (Drs Felger and Miller) jfelger@gmail.com.
authors: Jennifer C
authors: JC
authors: Felger
authors: Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA (Drs Felger, Hernandez, and Miller); The Winship Cancer Institute, Emory University, Atlanta, GA (Drs Felger and Miller).
authors: Carla R
authors: CR
authors: Hernandez
authors: Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA (Drs Felger, Hernandez, and Miller); The Winship Cancer Institute, Emory University, Atlanta, GA (Drs Felger and Miller).
authors: Andrew H
authors: AH
authors: Miller
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology*; D005260:Female; D016898:Interferon-alpha / Q000008:administration & dosage / Q000378:metabolism*; D007980:Levodopa / Q000494:pharmacology*; D008253:Macaca mulatta; D008297:Male; D017551:Microdialysis
chemical_list: D015259:Dopamine Agents; D016898:Interferon-alpha; D015102:3,4-Dihydroxyphenylacetic Acid; D007980:Levodopa; D004298:Dopamine
keywords: anhedonia; cytokines; depression; dopamine; in vivo microdialysis
references: Biol Psychiatry. 2009 Feb 15;65(4):296-303
references: 18801471
references: Brain Res. 2003 Jul 18;978(1-2):104-14
references: 12834904
references: Neuropsychopharmacology. 2013 Oct;38(11):2179-87
references: 23657438
references: JAMA Psychiatry. 2013 Jan;70(1):31-41
references: 22945416
references: Arch Gen Psychiatry. 2007 Mar;64(3):327-37
references: 17339521
references: J Biol Chem. 1999 Mar 19;274(12):8254-60
references: 10075731
references: J Clin Oncol. 2010 Aug 10;28(23):3673-9
references: 20625123
references: Neuropsychopharmacology. 2014 Feb;39(3):595-604
references: 23995581
references: Arch Gen Psychiatry. 2012 Oct;69(10):1044-53
references: 23026954
references: Lancet. 2006 Jan 7;367(9504):29-35
references: 16399150
references: Front Neuroendocrinol. 2012 Aug;33(3):315-27
references: 23000204
references: Curr Drug Metab. 2008 Sep;9(7):622-7
references: 18781914
references: J Neurosci. 2009 Apr 1;29(13):4200-9
references: 19339614
references: J Neurochem. 2002 Jan;80(1):168-77
references: 11796755
references: BMJ Open. 2012 Dec 11;2(6):null
references: 23233700
references: J Neurosci. 2007 Jul 25;27(30):8138-48
references: 17652604
references: J Interferon Cytokine Res. 2012 May;32(5):216-20
references: 22191466
references: Biol Psychiatry. 2010 Oct 15;68(8):748-54
references: 20719303
references: J Clin Oncol. 2013 Jul 1;31(19):2421-7
references: 23690414
references: Neurosci Biobehav Rev. 2011 Jan;35(3):537-55
references: 20603146
references: J Neurochem. 1993 Jun;60(6):2175-80
references: 8492125
references: Biol Psychiatry. 2007 Dec 1;62(11):1324-33
references: 17678633
references: Biol Psychiatry. 2008 Jun 1;63(11):1022-9
references: 18242584
references: Brain Behav Immun. 2013 Jul;31:153-60
references: 23072726
references: Nature. 2013 Jan 24;493(7433):537-41
references: 23235822