Levodopa gains psychostimulant-like properties after nigral dopaminergic loss

Abstract

Dopamine dysregulation syndrome shares some core behavioral features with psychostimulant addiction, suggesting that dopamine replacement therapy can acquire psychostimulantlike properties in some patients with Parkinson disease (PD). We here report strong experimental evidence supporting this hypothesis in an α-synuclein rat model of PD. Although levodopa had no effect in controls, it acquired 2 prominent psychostimulantlike properties in Parkinsonian rats: (1) it produced intense reward on its own and in parallel (2) decreased interest in other nondrug reward. These 2 effects may combine to explain the addictive use of levodopa after loss of midbrain dopamine neurons in some PD patients.