Differences in release and clearance of extracellular dopamine in the striatum after spontaneous or GM1-ganglioside-stimulated recovery from experimental Parkinsonism

Abstract

Purpose: This study was designed to assess differences in dopamine clearance rates and potassium chloride (KCl)-stimulated release in the striatum of cats that had either spontaneously recovered from 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced Parkinsonism or recovered after receiving GM1 ganglioside treatment. Methods: A severe Parkinsonian motor disorder was produced in 17 adult cats by administration of MPTP for seven to ten days. Six MPTP-treated cats received daily GM1 administration (30 mg/kg, i.m.) for 6 weeks and eleven MPTP-treated cats were allowed to spontaneously recover over the same period of time. High-speed chronoamperometric electrochemical measurements were obtained from dorsal and ventral striatal regions in all animals. Dopamine clearance rates were obtained by measuring the clearance of pressure-ejected dopamine from the extracellular space and local potassium-induced release was studied by applying KCl to the tissue. Results: Dopamine clearance rates recorded in all striatal areas in GM1-treated cats were significantly faster than dopamine clearance rates recorded in spontaneously recovered cats. In GM1-treated animals, electrochemical signals recorded in response to KCl stimulation were sig-nificantly greater in all striatal areas compared to spontaneously recovered animals. Reduction/oxidation (redox) ratios recorded in GM1- treated animals indicated dopamine to be the predominant electroactive species released in all striatal areas in response to KCl stimulation. Redox ratios recorded in the ventral striatum of spontaneously recovered cats also indicated dopamine to be the predominant electroactive spe-cies released in response to KCl stimulation. However, redox ratios recorded in the dorsal striatum of spontaneosuly recovered cats indicated serotonin to significantly contribute to the recorded signal. Conclusions: These results support previous observations that volume transmission may predominate dopaminergic signaling in the stria-tum of spontaneously recovered cats and suggest that a greater degree of synaptic transmission is possible in GM1-treated animals. While the functional significance of this partial restoration of dopaminergic synaptic transmission in the striatum remains to be determined, it may under-lie improved behavioral recovery observed following GM1 treatment.