Locomotor response to l-DOPA in reserpine-treated rats following central inhibition of aromatic l-amino acid decarboxylase: Further evidence for non-dopaminergic actions of l-DOPA and its metabolites

l-DOPA is the most widely used treatment for Parkinson's disease. The anti-parkinsonian and pro-dyskinetic actions of l-DOPA are widely attributed to its conversion, by the enzyme aromatic l-amino acid decarboxylase (AADC), to dopamine. We investigated the hypothesis that exogenous l-DOPA can induce behavioural effects without being converted to dopamine in the reserpine-treated rat-model of Parkinson's disease. A parkinsonian state was induced with reserpine (3mg/kg s.c.). Eighteen hours later, the rats were administered l-DOPA plus the peripherally acting AADC inhibitor benserazide (25mg/kg), with or without the centrally acting AADC inhibitor NSD1015 (100mg/kg). l-DOPA/benserazide alone reversed reserpine-induced akinesia (4158±1125 activity counts/6h, cf vehicle 1327±227). Addition of NSD1015 elicited hyperactive behaviour that was approximately 7-fold higher than l-DOPA/benserazide (35755±5226, P