Preclinical studies in animal model

Preclinical studies in animal models of Parkinson’s disease19–22 indicate that both dopamine agonists and levodopa have reinforcing effects. Dopamine agonists with high affinity for D3R receptors and levodopa promote conditioned place-preference (whereby rodents prefer places associated with a reinforcing drug to places associated with a placebo) in several rat models of Parkinson’s disease, compared with control littermates (figure 2).19–21 This outcome was hypothesised to reflect postsynaptic dopamine receptor super-sensitivity because increased sensitivity of dopamine receptors was observed after the concentration of endogenous dopamine was reduced following the degeneration of dopamine neurons.