Pramipexole induced place preference after L-dopa therapy and nigral dopaminergic loss: linking behavior to transcriptional modifications.
Impulsive-compulsive disorders (ICD) in patients with Parkinson's disease (PD) have been described as behavioral or substance addictions including hypersexuality, gambling, or compulsive medication use of the dopamine replacement therapy (DRT).



A remaining challenge is to understand the neuroadaptations leading to reward bias in PD patients under DRT.



To this end, the appetitive effect of the D2/D3 agonist pramipexole was assessed after chronic exposure to L-dopa in an alpha-synuclein PD rat model.



Association of progressive nigral loss and chronic L-dopa was required to observe a pramipexole-induced place preference. This behavioral outcome was inhibited by metabotropic glutamate receptor 5 (mGluR5) antagonism while transcriptional profiling highlighted regulations potentially related to the context of psychostimulant addiction.



This study provides evidences strongly suggesting that PD-like lesion and L-dopa therapy were concomitant factors involved in striatal remodeling underlying the pramipexole-induced place preference. Molecular and pharmacological data suggest a key involvement of the glutamatergic pathway in this behavioral outcome.
UFR Medicine, Université d'Auvergne, 28 Place Henri Dunant, 63000, Clermont-Ferrand, France. simon.loiodice@gmail.com.|Department of Non-Clinical Development, UCB Biopharma SPRL, Chemin du Foriest 1, 1420, Braine-l'Alleud, Belgium. simon.loiodice@gmail.com.
Simon
S
Loiodice
Department of Non-Clinical Development, UCB Biopharma SPRL, Chemin du Foriest 1, 1420, Braine-l'Alleud, Belgium.|Faculty of Biological Sciences, University of Leeds, LS29JT, Leeds, UK.
Poppy
P
Winlow
Department of Non-Clinical Development, UCB Biopharma SPRL, Chemin du Foriest 1, 1420, Braine-l'Alleud, Belgium.|Euroscreen SA, 6041, Gosselies, Belgium.
Sarah
S
Dremier
Department of Non-Clinical Development, UCB Biopharma SPRL, Chemin du Foriest 1, 1420, Braine-l'Alleud, Belgium.
Etienne
E
Hanon
UFR Medicine, Université d'Auvergne, 28 Place Henri Dunant, 63000, Clermont-Ferrand, France.
David
D
Dardou
UFR Medicine, Université d'Auvergne, 28 Place Henri Dunant, 63000, Clermont-Ferrand, France.
Omar
O
Ouachikh
UFR Medicine, Université d'Auvergne, 28 Place Henri Dunant, 63000, Clermont-Ferrand, France.
Aziz
A
Hafidi
Department of Non-Clinical Development, UCB Biopharma SPRL, Chemin du Foriest 1, 1420, Braine-l'Alleud, Belgium.
Andre Nogueira
AN
da Costa
UFR Medicine, Université d'Auvergne, 28 Place Henri Dunant, 63000, Clermont-Ferrand, France.|Neurology Department, CHU de Clermont-Ferrand, 28 Place Henri Dunant, 63000, Clermont-Ferrand, France.
Franck
F
Durif
D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology* / Q000627:therapeutic use; D052160:Benzothiazoles / Q000494:pharmacology* / Q000627:therapeutic use; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004298:Dopamine / Q000378:metabolism; D005260:Female; D006801:Humans; D007175:Impulsive Behavior / Q000187:drug effects*; D007980:Levodopa / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D010302:Parkinson Disease, Secondary / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D000077487:Pramipexole; D051381:Rats; D064529:Receptor, Metabotropic Glutamate 5 / Q000378:metabolism*; D051844:alpha-Synuclein
D000978:Antiparkinson Agents; D052160:Benzothiazoles; D064529:Receptor, Metabotropic Glutamate 5; C497606:Snca protein, rat; D051844:alpha-Synuclein; D007980:Levodopa; D000077487:Pramipexole; D004298:Dopamine
Alpha-synuclein; Impulsive/compulsive disorders; L-dopa; Parkinson’s disease; Pramipexole; Transcriptional profiling