Drs. Favier and Duran contributed equally to this study.
Pramipexole reverses Parkinson's disease-related motivational deficits in rats
Version of Record online: 11 FEB 2014
© 2014 International Parkinson and Movement Disorder Society
Volume 29, Issue 7, pages 912–920, June 2014
How to Cite
Favier, M., Duran, T., Carcenac, C., Drui, G., Savasta, M. and Carnicella, S. (2014), Pramipexole reverses Parkinson's disease-related motivational deficits in rats. Mov. Disord., 29: 912–920. doi: 10.1002/mds.25837
Funding agencies: This work was supported by the Institut National de la Santé et de la Recherche Médicale, Fondation NeuroDis, Association France Parkinson, Région Rhône-Alpes (ARC no. 2), and Université Joseph Fourier.
Relevant conflicts of interest/financial disclosures: Nothing to report.
Full financial disclosures and author roles may be found in the online version of this article.
- Issue online: 12 JUN 2014
- Version of Record online: 11 FEB 2014
- Manuscript Accepted: 13 JAN 2014
- Manuscript Revised: 5 DEC 2013
- Manuscript Received: 26 JUL 2013
- Parkinson's disease;
- D2/D3 receptors
Recent evidence suggests that Parkinson's disease affects not only movement, but also cognitive and psychiatric functions. Among these nonmotor complications, apathy, which is defined as a lack of motivation and operationalized as a quantitative reduction in goal-directed behavior, may even precede motor impairments, disappearing with the introduction of dopaminergic (DA) therapies and possibly reappearing with its discontinuation, suggesting a causal role of DA. We recently developed a lesion-based model, with stereotaxic infusion of 6-hydroxydopamine (6-OHDA) into precise areas of the rat SNc or ventral tegmental area and showed, in several operant tasks, that a partial denervation of the nigrostriatal, but not of the mesocorticolimbic, DA system induced profound motivational deficits during instrumental action. We investigated the time course of the effects of nigrostriatal DA denervation on motivation in rats, by assessing the negative effect of SNc bilateral 6-OHDA infusion on preacquired operant behavior, and determining whether the induced deficits were sensitive to the introduction and withdrawal of a clinically relevant PD treatment, the DA D2/D3 receptor agonist, pramipexole (PRA). Partial nigrostriatal DA denervation was accompanied by a significant reduction in operant behavior. This deficit, indicative of a decrease in motivation, was fully reversed by PRA and reappeared after treatment withdrawal. This longitudinal preclinical study provides evidence for the implication of the DA nigrostriatal system in PD-associated apathy. Moreover, by showing a good isomorphy and predictive value, our model highlights the relevance of D2/D3 receptors as potential targets for alleviating apathy in PD. © 2014 International Parkinson and Movement Disorder Society