Related Experiment Videos
Increased midbrain dopaminergic cell activity following 2'CH3-MPTP-induced dopaminergic cell loss: an in vitro
G L Bernardini1, S G Speciale, D C German
1Department of Physiology, University of Texas Southwestern Medical Center, Dallas 75235-9070.
Abstract:
Several days after the administration of 1-methyl-4-(2'-methylphenyl)-1,2,3,6-tetrahydropyridine (2'CH3-MPTP) to the BALB/cJ mouse there is a loss of midbrain dopaminergic neurons, a reduction of forebrain dopamine (DA) content, and an elevation in forebrain DA turnover. The purpose of the present study was to determine whether the increase in forebrain DA turnover is related to an increase in dopaminergic neuronal activity. In vitro extracellular single unit recordings were made from midbrain dopaminergic neurons in the substantia nigra pars compacta (nucleus A9) and ventral tegmental area (nucleus A10) of BALB/cJ mice. The experimental animals were treated intraperitoneally with 40, 50 or 55 mg/kg 2'CH3-MPTP and killed 7-15 days later. Forebrain DA concentrations were decreased below control values by the two higher toxin doses in the caudate-putamen (67% and 78%, respectively), but not in the nucleus accumbens. DA turnover increased more than 2-fold in the caudate-putamen, but was unchanged in the nucleus accumbens. Nucleus A9 cells, in the 2'CH3-MPTP-treated animals, exhibited a 3-fold increase in the number of spontaneously active cells, and an 84% increase in basal firing rates. There was also a positive correlation between the A9 cell firing rates, and the DA turnover in the striatum of the toxin-treated mice. Nucleus A10 cells, in the 2'CH3-MPTP-treated animals, exhibited neither changes in number of spontaneously active cells nor changes in firing rates.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
The neurotoxin 2
Area of Science:
- Neuroscience
- Neuropharmacology
Background:
- 1-methyl-4-(2'-methylphenyl)-1,2,3,6-tetrahydropyridine (2'CH3-MPTP) induces dopaminergic neurotoxicity.
- Previous studies show loss of midbrain dopaminergic neurons and altered dopamine levels after 2'CH3-MPTP administration.
Purpose of the Study:
- To investigate if increased forebrain dopamine turnover is linked to enhanced dopaminergic neuronal activity.
- To examine the effects of 2'CH3-MPTP on dopaminergic neuron firing rates in vivo.
Main Methods:
- BALB/cJ mice were administered varying doses of 2'CH3-MPTP (40-55 mg/kg).
- Extracellular single unit recordings were performed on substantia nigra pars compacta (A9) and ventral tegmental area (A10) dopaminergic neurons.
- Dopamine concentrations and turnover were measured in forebrain regions 7-15 days post-treatment.
Main Results:
- 2'CH3-MPTP treatment significantly reduced dopamine in the caudate-putamen and increased dopamine turnover.
- Substantia nigra pars compacta (A9) neurons showed a 3-fold increase in spontaneous activity and an 84% increase in firing rate.
- A positive correlation was observed between A9 cell firing rates and striatal dopamine turnover.
Conclusions:
- Increased dopaminergic neuronal activity in the substantia nigra pars compacta contributes to elevated dopamine turnover in the striatum following 2'CH3-MPTP exposure.
- Ventral tegmental area (A10) neurons were not affected by the toxin.