The dopamine agonist piribedil with L-DOPA improves attentional dysfunction: relevance for Parkinson's disease.
Cognitive deficits are often associated with motor symptoms in Parkinson's disease. This study investigates the ability of piribedil ([(methylenedioxy-3,4 benzyl)-4 pyperazinyl-1]-2 pyrimidine), a D(2)/D(3) dopamine (DA) receptor agonist with antagonist activity at alpha(2A)-adrenoceptors, to restore motor and attentional deficits in nigrostriatal 6-hydroxydopamine-lesioned rats. Subjects were trained to depress a lever, detect a stimulus occurring after variable foreperiods, and release the lever quickly afterward. Striatal DA depletions produce deficits in the timing of foreperiods and prolong reaction times. Although a subchronic treatment with piribedil (0.1-2 mg/kg) is not effective, a dose of 0.3 mg/kg administered for 3 weeks significantly reverses the akinetic deficits produced by the striatal dopamine depletion and progressively improves attentional deficits. When coadministered with the dopamine prodrug l-3,4-dihydroxyphenylalanine (l-DOPA) (3 mg/kg), piribedil (0.3 mg/kg) promotes a rapid and full recovery of preoperative performance. These results suggest that administration of l-DOPA in combination with piribedil in a chronic treatment as either initial or supplemental therapy for Parkinson's disease might improve cognitive functions while reducing the risk for motor complications.
Turle-Lorenzo
Nathalie
N
Laboratoire de Neurobiologie de la Cognition, UMR 6155 Centre National de la Recherche Scientifique-Université de Provence, Case C, 3 Place Victor Hugo, 13331 Marseille cedex 3, France.
Maurin
Béatrice
B
Puma
Carole
C
Chezaubernard
Claire
C
Morain
Philippe
P
Baunez
Christelle
C
Nieoullon
André
A
Amalric
Marianne
M
D000818:Animals; D000978:Antiparkinson Agents / Q000627:therapeutic use*; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy*; D003071:Cognition / Q000187:drug effects; D003342:Corpus Striatum / Q000473:pathology; D018491:Dopamine Agonists / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D007980:Levodopa / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008454:Mazindol / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects; D010300:Parkinson Disease / Q000188:drug therapy; D010891:Piribedil / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects
D000978:Antiparkinson Agents; D018491:Dopamine Agonists; D007980:Levodopa; D008454:Mazindol; D010891:Piribedil