Systems NeuroscienceResearch PaperIn vivo dopamine release and uptake impairments in rats treated with 3-nitropropionic acid
Section snippets
Materials
3NP was obtained from Fluka (Sigma-Aldrich, St. Louis, MO, USA). Prior to administration to rats, 3NP was dissolved in water, adjusted to pH 7.3 with 5 M NaOH, and stabilized at pH 7.3-7.4 with 0.1 M phosphate-buffered saline.
Animals
Male Lewis rats (Charles River Laboratories, Inc., Wilmington, MA, USA), 12 weeks of age and weighing 300–350 g, were housed one per cage in plastic cages with food and water available ad libitum in a temperature/humidity-controlled environment on a 12-h light/dark cycle.
Striatal dopamine release is attenuated in 3NP-treated rats
We employed FSCV to measure the maximum amount of evoked dopamine release, [DA]max, in the striatum of rats that had been treated with 3NP for 5 days. Representative data are shown in Fig. 1. Immediately after the initiation of the series of 120 biphasic electrical stimulus pulses, dopamine release was detected by the carbon-fiber microelectrode in both sham rats and 3NP-treated rats. Cyclic voltammograms, placed above the stimulated release plots, confirm that the electroactive species is
Discussion
In this study, we examined the impact of systemic 3NP treatment on dopamine release and uptake in Lewis rats. Even though striatal dopamine content was unchanged, dopamine release ([DA]max) and the maximum rate of dopamine uptake (Vmax) were decreased in 3NP-treated rats compared to sham control rats. The Michaelis–Menten constant, Km, was unchanged by 3NP treatment. Dopamine release was impaired uniformly at multiple depths in the dorsal striatum and was not accompanied by the release of other
Conclusion
In summary, this work identifies deficiencies in dopamine release and uptake parameters, measured in vivo, in 3NP chemically-induced HD model rats. These deficiencies correlate with locomotor impairments. Studies aimed at understanding how changes in dopamine signaling contribute to behavior in HD have gained recent interest. Thus, given the extensive use of 3NP-treated HD model rats and the therapeutic potential of dopamine modulation in HD, it is important to clearly assess how dopamine
Acknowledgments
The authors acknowledge Prof. Emmanuel Brouillet, Unité de Researche Associée Commissariat à l'Energie Atomique, Orsay, France, for advice with the 3NP experimental protocol and Prof. R. Mark Wightman, University of North Carolina, Chapel Hill and Dr. Michael L. A. V. Heien, Penn State University, for TarHeel voltammetry software. The authors also acknowledge Prof. Stephen C. Fowler, University of Kansas, for advice on the behavioral experimentation. This research was supported by grants from
References (72)
- et al.
Chronic intoxication with 3-nitropropionic acid in rats induces the loss of striatal dopamine terminals without affecting nigral cell viability
Neurosci Lett
(2004) - et al.
Increased Alix (apoptosis-linked gene-2 interacting protein X) immunoreactivity in the degenerating striatum of rats chronically treated by 3-nitropropionic acid
Neurosci Lett
(2004) - et al.
Striatal and cortical neurochemical changes induced by chronic metabolic compromise in the 3-nitropropionic model of Huntington's disease
Neurobiol Dis
(2002) - et al.
Early exploratory behavior abnormalities in R6/1 Huntington's disease transgenic mice
Brain Res
(2004) - et al.
Replicating Huntington's disease phenotype in experimental animals
Prog Neurobiol
(1999) - et al.
Inactivation of succinate dehydrogenase by 3-nitropropionate
J Biol Chem
(1979) - et al.
ATP serves as a negative feedback inhibitor of voltage-gated Ca2+ channel currents in cultured bovine adrenal chromaffin cells
Neuron
(1996) - et al.
Amino acid neurotransmitters in postmortem human brain analyzed by high performance liquid chromatography with electrochemical detection
J Neurosci Methods
(1987) - et al.
Striatal dopamine depletion and behavioural sensitization induced by methamphetamine and 3-nitropropionic acid
Eur J Pharmacol
(1999) - et al.
A force-plate actometer for quantitating rodent behaviors: illustrative data on locomotion, rotation, spatial patterning, stereotypies, and tremor
J Neurosci Methods
(2001)