title: Levodopa gains psychostimulant-like properties after nigral dopaminergic loss.
abstract: Dopamine dysregulation syndrome shares some core behavioral features with psychostimulant addiction, suggesting that dopamine replacement therapy can acquire psychostimulantlike properties in some patients with Parkinson disease (PD). We here report strong experimental evidence supporting this hypothesis in an α-synuclein rat model of PD. Although levodopa had no effect in controls, it acquired 2 prominent psychostimulantlike properties in Parkinsonian rats: (1) it produced intense reward on its own and in parallel (2) decreased interest in other nondrug reward. These 2 effects may combine to explain the addictive use of levodopa after loss of midbrain dopamine neurons in some PD patients.
authors.affiliation: Institute of Neurodegenerative Diseases, UMR 5293, F-33000 Bordeaux, France, University of Bordeaux, Bordeaux, France; Institute of Neurodegenerative Diseases, UMR 5293, F-33000 Bordeaux, France, National Center for Scientific Research, Bordeaux, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Engeln
authors.forename: Stefania
authors.initials: S
authors.lastname: Fasano
authors.forename: Serge H
authors.initials: SH
authors.lastname: Ahmed
authors.forename: Martine
authors.initials: M
authors.lastname: Cador
authors.forename: Veerle
authors.initials: V
authors.lastname: Baekelandt
authors.forename: Erwan
authors.initials: E
authors.lastname: Bezard
authors.forename: Pierre-Olivier
authors.initials: PO
authors.lastname: Fernagut
mesh_terms: D000256:Adenoviridae / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology / Q000627:therapeutic use*; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000473:pathology*; D005518:Food Preferences / Q000187:drug effects; D006801:Humans; D007980:Levodopa / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D009154:Mutation / Q000235:genetics; D010300:Parkinson Disease / Q000188:drug therapy* / Q000209:etiology / Q000235:genetics / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D012201:Reward; D012439:Saccharin / Q000008:administration & dosage; D013378:Substantia Nigra / Q000473:pathology*; D013549:Sweetening Agents / Q000008:administration & dosage; D013649:Taste / Q000187:drug effects; D014161:Transduction, Genetic; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism; D051844:alpha-Synuclein / Q000235:genetics / Q000633:toxicity
chemical_list: D000978:Antiparkinson Agents; D013549:Sweetening Agents; D025801:Ubiquitin; D051844:alpha-Synuclein; D007980:Levodopa; D014446:Tyrosine 3-Monooxygenase; D012439:Saccharin