title: Direct and indirect striatal efferent pathways are differentially influenced by low and high dyskinetic drugs: behavioural and biochemical evidence.
abstract: Clinical evidence suggests that stimulation of the D(1) rather than D(2) dopamine receptor is related to the development of dyskinesias in Parkinson's disease (PD). We evaluated, in the 6-hydroxydopamine rat model of PD, sensitization of contralateral turning (SCT) behaviour and abnormal involuntary movements (AIMs) as behavioural parameters of dyskinetic response, and changes in zif-268 mRNA expression in striatonigral and striatopallidal neurons on subchronic administration of the D(2)/D(3) agonist ropinirole, defined as a mild dyskinetic drug in the clinic. Results were compared with previous findings on repeated L-dopa treatment. Ropinirole displayed a mild dyskinetic response characterized by SCT only, which contrasted with the presence of SCT in association with AIMs elicited by repeated L-dopa. Zif-268 mRNA levels were decreased in both striatonigral and striatopallidal neurons by ropinirole, in contrast to hyper-expression of zif-268 mRNA selectively induced by L-dopa in striatonigral neurons. Unbalanced responsiveness of striatal efferent neurons might represent a molecular correlate of high dyskinetic potential and AIMs in rats; in contrast, a balanced striatal output might underlie the low dyskinetic potential displayed by ropinirole.
authors.affiliation: Department of Toxicology, University of Cagliari, via Ospedale 72, Cagliari, Italy. acarta@unica.it
authors.forename: Anna R
authors.initials: AR
authors.lastname: Carta
authors.forename: Lucia
authors.initials: L
authors.lastname: Frau
authors.forename: Silvia
authors.initials: S
authors.lastname: Pontis
authors.forename: Annalisa
authors.initials: A
authors.lastname: Pinna
authors.forename: Micaela
authors.initials: M
authors.lastname: Morelli
mesh_terms: D000818:Animals; D000978:Antiparkinson Agents / Q000009:adverse effects / Q000494:pharmacology*; D001519:Behavior / Q000187:drug effects*; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology*; D003342:Corpus Striatum / Q000187:drug effects* / Q000502:physiology; D004195:Disease Models, Animal; D004409:Dyskinesia, Drug-Induced / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D004525:Efferent Pathways / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007980:Levodopa / Q000009:adverse effects / Q000494:pharmacology*; D016627:Oxidopamine / Q000633:toxicity; D010300:Parkinson Disease / Q000188:drug therapy / Q000209:etiology; D051381:Rats
chemical_list: D000978:Antiparkinson Agents; D007980:Levodopa; D016627:Oxidopamine