Comparison of intrastriatal administration of noradrenaline and l-DOPA on dyskinetic movements: a bilateral reverse in vivo microdialysis study in 6-hydroxydopamine-lesioned rats.
l-DOPA-induced dyskinesia is known as involuntary debilitating movement, which limits quality of life in patients suffering from Parkinson's disease. The present study focuses on the role of the neurotransmitter noradrenaline (NA) on dyskinetic movements in comparison to the effect of l-DOPA. Rats were unilaterally lesioned with 6-hydroxydopamine and treated with l-DOPA/benserazide (6/15 mg/kg, p.o.) to induce stable dyskinetic movements. On the day of the experiment, NA (0.04 nmol/min, 0.4 nmol/min) and l-DOPA (0.04 nmol/min, 0.4 nmol/min) were perfused into the lesioned and non-lesioned striatum of dyskinetic rats using the reverse in vivo microdialysis technique. Neither NA nor l-DOPA treatment of the non-lesioned striatum produced any dyskinetic behavior. In contrast, administration of l-DOPA 0.4 nmol/min into the lesioned striatum led to a significant increase in dyskinesia indicated by abnormal axial, limb and orolingual movements. Notably, perfusion with NA 0.4 nmol/min into the lesioned striatum revealed a highly significant induction of dyskinetic movements, which are similar to the dyskinesia subtype profile of l-DOPA. In conclusion, NA is as potent as l-DOPA to express dyskinetic movements in l-DOPA-primed rats.
Buck
K
K
Department of CNS Diseases Research, Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Strasse 65, 88397 Biberach, Germany.
Ferger
B
B
D000704:Analysis of Variance; D000818:Animals; D001545:Benserazide / Q000009:adverse effects; D003342:Corpus Striatum / Q000187:drug effects*; D004195:Disease Models, Animal; D015259:Dopamine Agents / Q000008:administration & dosage* / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D004409:Dyskinesia, Drug-Induced / Q000188:drug therapy* / Q000209:etiology; D007980:Levodopa / Q000009:adverse effects* / Q000627:therapeutic use*; D008297:Male; D017551:Microdialysis; D009638:Norepinephrine / Q000008:administration & dosage*; D016627:Oxidopamine; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000188:drug therapy; D051381:Rats; D017208:Rats, Wistar; D012720:Severity of Illness Index
D015259:Dopamine Agents; D007980:Levodopa; D001545:Benserazide; D016627:Oxidopamine; D009638:Norepinephrine