Motor regulation system in a Parkinson's disease animal model

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In large doses, levodopa decreases the firing rate of rat dopaminergic neurons in the substantia nigrapars compacta (SNC DA). This phenomenon may be due to a negative feedback mechanism through autoreceptors within the substantia nigra. Whether chronic levodopa administration influences on SNC DA remain unclear. We evaluated SNC DA function using the firing rate and dopaminergic terminal excitability of dopamine neurons in male Sprague-Dawley rats. Two groups of animals ; the first group (n=19 rats) received daily intraperitoneal injection of levodopa (100mg/kg) and carbidopa (25mg/kg) for 60 days, while the second group (n=27) was the control. Extracellular single unit recordings of SNC DA were obtained with micropipettes. Dopaminergic terminal excitability was determined as the threshold of antidromic responses evoked by neostriatal electrostimulation. There were no significant differences in the firing rate between two groups, but the levodopa group showed a decrease in the terminal excitability compared with that in the control group. The decrease of terminal excitability may be related to impare striatal dopamine release. This finding appears to be related the clinical observation that L-dopa therapeutic response diminishes following chronic treatment.