title: Striatal activation by optogenetics induces dyskinesias in the 6-hydroxydopamine rat model of Parkinson disease.
abstract: Long-term levodopa (l-dopa) treatment is associated with the development of l-dopa-induced dyskinesias in the majority of patients with Parkinson disease (PD). The etiopathogonesis and mechanisms underlying l-dopa-induced dyskinesias are not well understood.
  
  
  
  We used striatal optogenetic stimulation to induce dyskinesias in a hemiparkinsonian model of PD in rats. Striatal dopamine depletion was induced unilaterally by 6-hydroxydopamine injection into the medial forebrain bundle. For the optogenetic manipulation, we injected adeno-associated virus particles expressing channelrhodopsin to stimulate striatal medium spiny neurons with a laser source.
  
  
  
  Simultaneous optical activation of medium spiny neurons of the direct and indirect striatal pathways in the 6-hydroxydopamine lesion but l-dopa naïve rats induced involuntary movements similar to l-dopa-induced dyskinesias, labeled here as optodyskinesias. Noticeably, optodyskinesias were facilitated by l-dopa in animals that did not respond initially to the laser stimulation. In general, optodyskinesias lasted while the laser stimulus was applied, but in some instances remained ongoing for a few seconds after the laser was off. Postmortem tissue analysis revealed increased FosB expression, a molecular marker of l-dopa-induced dyskinesias, primarily in medium spiny neurons of the direct pathway in the dopamine-depleted hemisphere.
  
  
  
  Selective optogenetic activation of the dorsolateral striatum elicits dyskinesias in the 6-hydroxydopamine rat model of PD. This effect was associated with a preferential activation of the direct striato-nigral pathway. These results potentially open new avenues in the understanding of mechanisms involved in l-dopa-induced dyskinesias. © 2017 International Parkinson and Movement Disorder Society.
authors.affiliation: HM-CINAC, Hospital Universitario HM Puerta del Sur, Mostoles and Medical School, CEU-San Pablo University, Madrid, Spain.|CIBERNED, Instituto Carlos III, Madrid, Spain.
authors.forename: Ledia
authors.initials: L
authors.lastname: F Hernández
authors.affiliation: HM-CINAC, Hospital Universitario HM Puerta del Sur, Mostoles and Medical School, CEU-San Pablo University, Madrid, Spain.
authors.forename: Ivan
authors.initials: I
authors.lastname: Castela
authors.affiliation: CIBERNED, Instituto Carlos III, Madrid, Spain.|Instituto Cajal-CSIC, Madrid, Spain.
authors.forename: Irene
authors.initials: I
authors.lastname: Ruiz-DeDiego
authors.affiliation: HM-CINAC, Hospital Universitario HM Puerta del Sur, Mostoles and Medical School, CEU-San Pablo University, Madrid, Spain.|CIBERNED, Instituto Carlos III, Madrid, Spain.
authors.forename: Jose A
authors.initials: JA
authors.lastname: Obeso
authors.affiliation: CIBERNED, Instituto Carlos III, Madrid, Spain.|Instituto Cajal-CSIC, Madrid, Spain.
authors.forename: Rosario
authors.initials: R
authors.lastname: Moratalla
mesh_terms: D018663:Adrenergic Agents / Q000633:toxicity*; D000818:Animals; D000978:Antiparkinson Agents / Q000009:adverse effects; D001921:Brain / Q000378:metabolism; D000075402:Channelrhodopsins; D003342:Corpus Striatum / Q000378:metabolism*; D004195:Disease Models, Animal; D004399:Dynorphins / Q000378:metabolism; D020820:Dyskinesias / Q000209:etiology*; D007839:Functional Laterality; D007980:Levodopa / Q000009:adverse effects; D008297:Male; D062308:Optogenetics / Q000009:adverse effects*; D016627:Oxidopamine / Q000633:toxicity*; D010300:Parkinson Disease / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014161:Transduction, Genetic; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D018663:Adrenergic Agents; D000978:Antiparkinson Agents; D000075402:Channelrhodopsins; C483820:Fosb protein, rat; D016760:Proto-Oncogene Proteins c-fos; D007980:Levodopa; D004399:Dynorphins; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase
keywords: Parkinson disease; dyskinesias; l-dopa; medium spiny neurons; optogenetics