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Dopamine uptake through the norepinephrine transporter in brain regions with low levels of the dopamine transporter: evidence from knock-out mouse lines.
J Neurosci. 2002 Jan 15; 22(2):389-95.JN

Abstract

Selective blockers of the norepinephrine transporter (NET) inhibit dopamine uptake in the prefrontal cortex. This suggests that dopamine in this region is normally cleared by the somewhat promiscuous NET. We have tested this hypothesis by comparing the effects of inhibitors selective for the three monoamine transporters with those of a nonspecific inhibitor, cocaine, on uptake of 3H-dopamine into synaptosomes from frontal cortex, caudate nucleus, and nucleus accumbens from wild-type, NET, and dopamine transporter (DAT) knock-out mice. Dopamine uptake was inhibited by cocaine and nisoxetine, but not by GBR12909, in frontal cortex synaptosomes from wild-type or DAT knock-out mice. At transporter-specific concentrations, nisoxetine and GBR12909 failed to block dopamine uptake into frontal cortex synaptosomes from NET knock-out mice. The efficacy of cocaine at the highest dose (1 mm) was normal in DAT knock-out mice but reduced by 70% in NET knock-out mice. Nisoxetine inhibited dopamine uptake by 20% in caudate and nucleus accumbens synaptosomes from wild-type and DAT knock-out mice but had no effect in those from NET knock-out mice. Cocaine failed to block dopamine uptake into caudate or nucleus accumbens synaptosomes from DAT knock-out mice. Cocaine and GBR12909 each inhibited dopamine uptake into caudate synaptosomes from NET knock-out mice, but cocaine effectiveness was reduced in the case of nucleus accumbens synaptosomes. Thus, whereas dopamine uptake in caudate and nucleus accumbens depends primarily on the DAT, dopamine uptake in frontal cortex depends primarily on the NET. These data underscore the fact that which transporter clears dopamine from a given region depends on both the affinities and the local densities of the transporters.

Authors+Show Affiliations

Behavioral Neuroscience Branch, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland 21224, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

11784783

Citation

Morón, Jose A., et al. "Dopamine Uptake Through the Norepinephrine Transporter in Brain Regions With Low Levels of the Dopamine Transporter: Evidence From Knock-out Mouse Lines." The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, vol. 22, no. 2, 2002, pp. 389-95.
Morón JA, Brockington A, Wise RA, et al. Dopamine uptake through the norepinephrine transporter in brain regions with low levels of the dopamine transporter: evidence from knock-out mouse lines. J Neurosci. 2002;22(2):389-95.
Morón, J. A., Brockington, A., Wise, R. A., Rocha, B. A., & Hope, B. T. (2002). Dopamine uptake through the norepinephrine transporter in brain regions with low levels of the dopamine transporter: evidence from knock-out mouse lines. The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, 22(2), 389-95.
Morón JA, et al. Dopamine Uptake Through the Norepinephrine Transporter in Brain Regions With Low Levels of the Dopamine Transporter: Evidence From Knock-out Mouse Lines. J Neurosci. 2002 Jan 15;22(2):389-95. PubMed PMID: 11784783.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dopamine uptake through the norepinephrine transporter in brain regions with low levels of the dopamine transporter: evidence from knock-out mouse lines. AU - Morón,Jose A, AU - Brockington,Alicia, AU - Wise,Roy A, AU - Rocha,Beatriz A, AU - Hope,Bruce T, PY - 2002/1/11/pubmed PY - 2002/1/31/medline PY - 2002/1/11/entrez SP - 389 EP - 95 JF - The Journal of neuroscience : the official journal of the Society for Neuroscience JO - J Neurosci VL - 22 IS - 2 N2 - Selective blockers of the norepinephrine transporter (NET) inhibit dopamine uptake in the prefrontal cortex. This suggests that dopamine in this region is normally cleared by the somewhat promiscuous NET. We have tested this hypothesis by comparing the effects of inhibitors selective for the three monoamine transporters with those of a nonspecific inhibitor, cocaine, on uptake of 3H-dopamine into synaptosomes from frontal cortex, caudate nucleus, and nucleus accumbens from wild-type, NET, and dopamine transporter (DAT) knock-out mice. Dopamine uptake was inhibited by cocaine and nisoxetine, but not by GBR12909, in frontal cortex synaptosomes from wild-type or DAT knock-out mice. At transporter-specific concentrations, nisoxetine and GBR12909 failed to block dopamine uptake into frontal cortex synaptosomes from NET knock-out mice. The efficacy of cocaine at the highest dose (1 mm) was normal in DAT knock-out mice but reduced by 70% in NET knock-out mice. Nisoxetine inhibited dopamine uptake by 20% in caudate and nucleus accumbens synaptosomes from wild-type and DAT knock-out mice but had no effect in those from NET knock-out mice. Cocaine failed to block dopamine uptake into caudate or nucleus accumbens synaptosomes from DAT knock-out mice. Cocaine and GBR12909 each inhibited dopamine uptake into caudate synaptosomes from NET knock-out mice, but cocaine effectiveness was reduced in the case of nucleus accumbens synaptosomes. Thus, whereas dopamine uptake in caudate and nucleus accumbens depends primarily on the DAT, dopamine uptake in frontal cortex depends primarily on the NET. These data underscore the fact that which transporter clears dopamine from a given region depends on both the affinities and the local densities of the transporters. SN - 1529-2401 UR - https://www.unboundmedicine.com/medline/citation/11784783/Dopamine_uptake_through_the_norepinephrine_transporter_in_brain_regions_with_low_levels_of_the_dopamine_transporter:_evidence_from_knock_out_mouse_lines_ L2 - http://www.jneurosci.org/cgi/pmidlookup?view=long&pmid=11784783 DB - PRIME DP - Unbound Medicine ER -