Abstract
Amantadine is used in the symptomatic treatment of Parkinson's disease to improve the akinesia and rigidity associated with this neurodegenerative disorder. Amantadine acts on the synthesis and release of dopamine (DA). In order to further characterize its mechanism of action, the drug was administered to MPTP‐treated mice which were used as a model of the neurochemical deficits associated with Parkinson's disease. The DA turnover in corpus striatum was evaluated. Adult male Swiss albino mice were injected ip with 12.5 mg/kg (82.6 μmol/kg) or 25 mg/kg (165 μmol/kg) of amantadine and 30 min later with MPTP (30 mg/kg, 143 μmol/kg). Both the amantadine and MPTP treatments were repeated for 3 consecutive days. Groups of mice were treated with amantadine or MPTP alone. Seven days after the last injection of drugs, the striatal content of DA and homovanillic acid (HVA) were measured by HPLC‐EC analysis. Additional groups of mice were treated with 3 consecutive daily doses of MPTP (30 mg/kg, 143 μmol/kg) and 7 days after the last administration received a single dose of amantadine at 25 mg/kg (165 μmol/kg). Turnover rate was measured by HVA content determination. The results indicate that amantadine induced a significantly increased striatal DA turnover rate (34%) in MPTP‐treated animals as compared with those animals treated with only MPTP. © 1993 Wiley‐Liss, Inc.