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

Purpose: This study was designed to assess differences in dopamine clearanc e 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 receivin g 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 rec eived 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 obta ined from dorsal and ventral striatal regions in all animals. Dopamine clea rance rates were obtained by measuring the clearance of pressure-ejected do pamine 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-tre ated cars were significantly faster than dopamine clearance rates recorded in spontaneously recovered cats. In GM1-treated animals, electrochemical si gnals recorded in response to KCl stimulation were significantly 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 stria tum of spontaneously recovered cats also indicated dopamine to be the predo minant electroactive species released in response to KCl stimulation. Howev er, redox ratios recorded in the dorsal striatum of spontaneosuly recovered cats indicated serotonin to significantly contribute to the recorded signa l. Conclusions: These results support previous observations that volume transm ission may predominate dopaminergic signaling in the striatum of spontaneou sly recovered cats and suggest that a greater degree of synaptic transmissi on is possible in GM1-treated animals. While the functional significance of this partial restoration of dopaminergic synaptic transmission in the stri atum remains to be determined, it may underlie improved behavioral recovery observed following GM1 treatment.