Evaluation of rewarding properties of pramipexole in a rat model of Parkinson’s disease: role of genetic background

Espa E;Pisanu A;MASALA, CARLA;Di Chiara G;FENU, SANDRO

2015-01-01

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Abstract

Pramipexole (PPX) is a dopamine (DA) D3/D2 receptors agonist widely used as DA replacement therapy (DRT) in the treatment of Parkinson’s disease (PD). However, its use has been related to the development of addictive-like behaviors associated to the DA dysregulation syndrome (DDS), particularly in a subpopulation of treated patients, characterized by impulsive-compulsive personality traits as well as previous histories of addiction. In order to assess such correlation between PPX treatment, impulsive-compulsive personality, PD and the onset of DDS, we studied the effects of PPX on conditioned place preference (CPP) paradigm, after bilateral 6-OHDA lesion of DA striatal terminals, in three different strains of rats: the addiction prone Lewis (LEW) and the addiction resistant Fisher 344 (F344) inbred strains, and the Sprague Dawley (SD) outbred strain. Further, in order to test its rewarding properties PPX was directly infused in the nucleus accumbens shell (NAc), a DA mesolimbic region known to be involved in the rewarding effects of drugs of abuse, in healthy rats belonging to the above mentioned strains. PPX (1 mg/kg s.c.) was able to induce a significant CPP in SD and LEW lesioned rats but not in F344 and control rats. When injected into the NAc shell, PPX (0,05 µg/0.5 µl) induced CPP in all rat strains, with differences in the persistence of its effect, which was stronger in Lewis compared to SD and F344 rats. These results suggest that in lesioned rats, the parkinsonian state boosts the rewarding properties of systemic PPX, which do not seem entirely influenced by genetic background. This may be due to the fact that PPX exhibits intrinsic rewarding properties as demonstrated by the induction of CPP in all the strains studied, when the drug has been infused directly in the shell of the NAc.