RT Journal Article SR Electronic T1 Dopaminergic neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in the mouse: an in vivo electrochemical study. JF Journal of Pharmacology and Experimental Therapeutics JO J Pharmacol Exp Ther FD American Society for Pharmacology and Experimental Therapeutics SP 259 OP 265 VO 235 IS 1 A1 G Gerhardt A1 G Rose A1 I Strömberg A1 G Conboy A1 L Olson A1 G Jonsson A1 B Hoffer YR 1985 UL http://jpet.aspetjournals.org/content/235/1/259.abstract AB The long-term (i.e., 4-5 months) effects of large doses (3 X 50 mg/kg) of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on striatal dopamine-containing afferents were studied in the NMRI strain of mice. Recently improved in vivo electrochemical methods were first used to examine the magnitude, spatial distribution and temporal dynamics of monoamine release initiated via local application of potassium in various regions of the mouse striatum. Immunohistochemical localization of tyrosine hydroxylase and computer-based image analysis were also used to quantitate regional catecholamine-containing nerve fiber densities in the caudate nucleus. The in vivo electrochemical studies showed a statistically significant decrease in the average potassium-evoked release of electroactive species from the MPTP-treated mouse caudate nucleus vs. control. Greater decreases in release were seen in dorsal than in ventral striatum (55% vs. 33%). The average rise time of potassium-evoked release was also significantly prolonged (greater than 50%) after MPTP pretreatment. Histochemical studies showed an overall reduction in the density of dopamine-containing terminals in the drug-treated mice, with a greater loss observed in the more dorsal regions of the caudate nucleus. The experimental data thus support a long-term selective destruction of dorsal vs. ventral dopamine-containing afferents to the striatum by the neurotoxin MPTP in mice.