Motivational properties of D2 and D3 dopamine receptors agonists and cocaine, but not with D1 dopamine receptors agonist and l-dopa, in bilateral 6-OHDA-lesioned rat

Abstract

Dopamine dysregulation syndrome in Parkinson's disease (PD) has been attributed to dopamine replacement therapy (DRT). We hypothesize that DRT can induce a potential rewarding effect in an animal model of PD.Using the conditioned place preference (CPP) paradigm, we investigated the motivational effects of l-dopa, dopamine receptor agonists (DRAs), and cocaine in rat with a bilateral 6-OHDA lesion of the nigrostriatal dopaminergic pathway.In 6-OHDA animals, D1 receptors agonist (SKF81297) revealed significantly a conditioned place aversion (CPA) at 3 mg/kg and 9 mg/kg doses. D2 receptors agonist (bromocriptine) induced both CPP and CPA at 1 mg/kg and 10 mg/kg doses respectively. D3 receptors agonist (PD128907) induced a CPP only at 1 mg/kg, comparable to that of cocaine. Sham animals revealed biphasic CPP curves, with significant dose effect, for the intermediate dose of the 3 DRAs. However, l-dopa induced no significant effect while cocaine induced CPP in both lesioned and sham animals.In conclusion, this study confirms the predominant roles of D2R class, and most specifically D3R subtypes, in rewarding properties of DRT.