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Presynaptic action of neurotensin on dopamine release through inhibition of D(2 )receptor function

BACKGROUND: Neurotensin (NT) is known to act on dopamine (DA) neurons at the somatodendritic level to regulate cell firing and secondarily enhance DA release. In addition, anatomical and indirect physiological data suggest the presence of NT receptors at the terminal level. However, a clear demonstr...

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Autores principales: Fawaz, Charbel S, Martel, Philippe, Leo, Damiana, Trudeau, Louis-Eric
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2745416/
https://www.ncbi.nlm.nih.gov/pubmed/19682375
http://dx.doi.org/10.1186/1471-2202-10-96
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author Fawaz, Charbel S
Martel, Philippe
Leo, Damiana
Trudeau, Louis-Eric
author_facet Fawaz, Charbel S
Martel, Philippe
Leo, Damiana
Trudeau, Louis-Eric
author_sort Fawaz, Charbel S
collection PubMed
description BACKGROUND: Neurotensin (NT) is known to act on dopamine (DA) neurons at the somatodendritic level to regulate cell firing and secondarily enhance DA release. In addition, anatomical and indirect physiological data suggest the presence of NT receptors at the terminal level. However, a clear demonstration of the mechanism of action of NT on dopaminergic axon terminals is lacking. We hypothesize that NT acts to increase DA release by inhibiting the function of terminal D2 autoreceptors. To test this hypothesis, we used fast-scan cyclic voltammetry (FCV) to monitor in real time the axonal release of DA in the nucleus accumbens (NAcc). RESULTS: DA release was evoked by single electrical pulses and pulse trains (10 Hz, 30 pulses). Under these two stimulation conditions, we evaluated the characteristics of DA D(2 )autoreceptors and the presynaptic action of NT in the NAcc shell and shell/core border region. The selective agonist of D(2 )autoreceptors, quinpirole (1 μM), inhibited DA overflow evoked by both single and train pulses. In sharp contrast, the selective D(2 )receptor antagonist, sulpiride (5 μM), strongly enhanced DA release triggered by pulse trains, without any effect on DA release elicited by single pulses, thus confirming previous observations. We then determined the effect of NT (8–13) (100 nM) and found that although it failed to increase DA release evoked by single pulses, it strongly enhanced DA release evoked by pulse trains that lead to prolonged DA release and engage D(2 )autoreceptors. In addition, initial blockade of D(2 )autoreceptors by sulpiride considerably inhibited further facilitation of DA release generated by NT (8–13). CONCLUSION: Taken together, these data suggest that NT enhances DA release principally by inhibiting the function of terminal D(2 )autoreceptors and not by more direct mechanisms such as facilitation of terminal calcium influx.
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spelling pubmed-27454162009-09-17 Presynaptic action of neurotensin on dopamine release through inhibition of D(2 )receptor function Fawaz, Charbel S Martel, Philippe Leo, Damiana Trudeau, Louis-Eric BMC Neurosci Research Article BACKGROUND: Neurotensin (NT) is known to act on dopamine (DA) neurons at the somatodendritic level to regulate cell firing and secondarily enhance DA release. In addition, anatomical and indirect physiological data suggest the presence of NT receptors at the terminal level. However, a clear demonstration of the mechanism of action of NT on dopaminergic axon terminals is lacking. We hypothesize that NT acts to increase DA release by inhibiting the function of terminal D2 autoreceptors. To test this hypothesis, we used fast-scan cyclic voltammetry (FCV) to monitor in real time the axonal release of DA in the nucleus accumbens (NAcc). RESULTS: DA release was evoked by single electrical pulses and pulse trains (10 Hz, 30 pulses). Under these two stimulation conditions, we evaluated the characteristics of DA D(2 )autoreceptors and the presynaptic action of NT in the NAcc shell and shell/core border region. The selective agonist of D(2 )autoreceptors, quinpirole (1 μM), inhibited DA overflow evoked by both single and train pulses. In sharp contrast, the selective D(2 )receptor antagonist, sulpiride (5 μM), strongly enhanced DA release triggered by pulse trains, without any effect on DA release elicited by single pulses, thus confirming previous observations. We then determined the effect of NT (8–13) (100 nM) and found that although it failed to increase DA release evoked by single pulses, it strongly enhanced DA release evoked by pulse trains that lead to prolonged DA release and engage D(2 )autoreceptors. In addition, initial blockade of D(2 )autoreceptors by sulpiride considerably inhibited further facilitation of DA release generated by NT (8–13). CONCLUSION: Taken together, these data suggest that NT enhances DA release principally by inhibiting the function of terminal D(2 )autoreceptors and not by more direct mechanisms such as facilitation of terminal calcium influx. BioMed Central 2009-08-14 /pmc/articles/PMC2745416/ /pubmed/19682375 http://dx.doi.org/10.1186/1471-2202-10-96 Text en Copyright © 2009 Fawaz et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Fawaz, Charbel S
Martel, Philippe
Leo, Damiana
Trudeau, Louis-Eric
Presynaptic action of neurotensin on dopamine release through inhibition of D(2 )receptor function
title Presynaptic action of neurotensin on dopamine release through inhibition of D(2 )receptor function
title_full Presynaptic action of neurotensin on dopamine release through inhibition of D(2 )receptor function
title_fullStr Presynaptic action of neurotensin on dopamine release through inhibition of D(2 )receptor function
title_full_unstemmed Presynaptic action of neurotensin on dopamine release through inhibition of D(2 )receptor function
title_short Presynaptic action of neurotensin on dopamine release through inhibition of D(2 )receptor function
title_sort presynaptic action of neurotensin on dopamine release through inhibition of d(2 )receptor function
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2745416/
https://www.ncbi.nlm.nih.gov/pubmed/19682375
http://dx.doi.org/10.1186/1471-2202-10-96
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