Motor impulsivity and delay intolerance are elicited in a dose-dependent manner with a dopaminergic agonist in parkinsonian rats

• Published in: Psychopharmacology 2020-08, Vol.237 (8), p.2419-2431
• Main Authors: Jiménez-Urbieta, Haritz, Gago, Belén, Quiroga-Varela, Ana, Rodríguez-Chinchilla, Tatiana, Merino-Galán, Leyre, Delgado-Alvarado, Manuel, Navalpotro-Gómez, Irene, Belloso-Iguerategui, Arantzazu, Marin, Concepció, Rodríguez-Oroz, María C.
• Format: Article
• Language: English
• Subjects: Agonists; Animal models; Basal ganglia; Biomedical and Life Sciences; Biomedicine; Central nervous system diseases; Denervation; Dopamine receptors; Drug addiction; Impulsive behavior; Impulsivity; Intolerance; Movement disorders; Neostriatum; Neurodegenerative diseases; Neurosciences; Original Investigation; Parkinson's disease; Pathophysiology; Pharmacology/Toxicology; Pramipexole; Psychiatry
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-020-05544-6

Rationale Impulse control disorders (ICD) and other impulsive-compulsive behaviours are frequently found in Parkinson’s disease (PD) patients treated with dopaminergic agonists. To date, there are no available animal models to investigate their pathophysiology and determine whether they can be elicited by varying doses of dopaminergic drugs. In addition, there is some controversy regarding the predispositional pattern of striatal dopaminergic depletion. Objectives To study the effect of two doses of pramipexole (PPX) on motor impulsivity, delay intolerance and compulsive-like behaviour. Methods Male rats with mild dopaminergic denervation in the dorsolateral striatum (bilateral injections of 6-hydroxidopamine (6-OHDA)) treated with two doses of PPX (0.25 mg/kg and 3 mg/kg) and tested in the variable delay-to-signal paradigm. Results Partial (50%) dopaminergic depletion did not induce significant changes in motor impulsivity or delay intolerance. However, 0.25 mg/kg of PPX increased motor impulsivity, while 3 mg/kg of PPX increased both motor impulsivity and delay intolerance. These effects were independent of the drug’s antiparkinsonian effects. Importantly, impulsivity scores before and after dopaminergic lesion were positively associated with the impulsivity observed after administering 3 mg/kg of PPX. No compulsive-like behaviour was induced by PPX administration. Conclusions We described a rat model, with a moderate dorsolateral dopaminergic lesion resembling that suffered by patients with early PD, that develops different types of impulsivity in a dose-dependent manner dissociated from motor benefits when treated with PPX. This model recapitulates key features of abnormal impulsivity in PD and may be useful for deepening our understanding of the pathophysiology of ICD.