Pramipexole induced place preference after L-dopa therapy and nigral dopaminergic loss: linking behavior to...

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.