The anterior caudate nucleus supports impulsive choices triggered by pramipexole

• Published in: Movement disorders Vol. 35; no. 2; pp. 296 - 305
• Main Authors: Martinez, Eva, Pasquereau, Benjamin, Saga, Yosuke, Météreau, Élise, Tremblay, Léon
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01.02.2020; Wiley Subscription Services, Inc; Wiley
• Subjects: Animals; Benzothiazoles - therapeutic use; Caudate nucleus; Cortex; decision making; Dopamine; Dopamine Agonists - therapeutic use; Haplorhini; Impulsive behavior; Impulsive Behavior - drug effects; impulsivity; Innervation; Life Sciences; Movement disorders; Neostriatum; Neurons and Cognition; nonhuman primate; Parkinson Disease - drug therapy; Parkinson's disease; Parkinsonian Disorders - drug therapy; Patients; PET imaging; Pramipexole; Pramipexole - pharmacology; Putamen; Restless legs syndrome; Reward; striatum; Ventral Striatum - drug effects; impulsivity; nonhuman primate; PET imaging; striatum; decision making
• ISSN: 0885-3185; 1531-8257; 1531-8257
• DOI: 10.1002/mds.27898

Background Pramipexole is a dopamine agonist used as a treatment in PD and restless legs syndrome to reduce motor symptoms, but it often induces impulse control disorders. In particular, patients with impulse control disorders tend to make more impulsive choices in the delay discounting task, that is, they choose small immediate rewards over larger delayed ones more often than patients without impulse control disorders and healthy subjects do. Yet the site of action of pramipexole that produces these impulsive choices remains unknown. Based on the heterogeneity of corticostriatal projections and the massive dopamine innervation of the striatum, we hypothesized that impulsive choices triggered by dopamine treatments may be supported by a specific striatal territory. OBJECTIVES This study aims to determine by which anteriorstriatum territory the Pramipexole trigger impulsive choices; the caudate nucleus, the ventral striatum or the putamen. METHODS We compared pramipexole intramuscular injections to intracerebral microinjections within the three striatal territories in healthy monkeys trained to execute the delay discounting task, a behavioral paradigm typically used to evaluate impulsive choices. RESULTS We found that pramipexole intramuscular injections induced impulsive choices in all monkeys. Local microinjections were performed inside the anterior caudate nucleus, ventral striatum, and anterior putamen and reproduced those impulsive choices when pramipexole was directly injected into the caudate nucleus, whereas injections into the ventral striatum or putamen had no effect on monkeys’ choices. CONCLUSIONS These results, consistent with clinical studies, suggest that impulsive choices triggered by pramipexole are supported by the caudate nucleus, allowing us to emphasize the importance of dopamine modulation inside this striatal territory in decision processes underlying impulsive behaviors. © 2019 International Parkinson and Movement Disorder Society