Presynaptic action of neurotensin on dopamine release through inhibition of D<sub>2 </sub>receptor function
<p>Abstract</p> <p>Background</p> <p>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 rec...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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BMC
2009-08-01
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| Series: | BMC Neuroscience |
| Online Access: | http://www.biomedcentral.com/1471-2202/10/96 |
| _version_ | 1818916658297700352 |
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| author | Trudeau Louis-Eric Leo Damiana Martel Philippe Fawaz Charbel S |
| author_facet | Trudeau Louis-Eric Leo Damiana Martel Philippe Fawaz Charbel S |
| author_sort | Trudeau Louis-Eric |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>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).</p> <p>Results</p> <p>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<sub>2 </sub>autoreceptors and the presynaptic action of NT in the NAcc shell and shell/core border region. The selective agonist of D<sub>2 </sub>autoreceptors, quinpirole (1 μM), inhibited DA overflow evoked by both single and train pulses. In sharp contrast, the selective D<sub>2 </sub>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<sub>2 </sub>autoreceptors. In addition, initial blockade of D<sub>2 </sub>autoreceptors by sulpiride considerably inhibited further facilitation of DA release generated by NT (8–13).</p> <p>Conclusion</p> <p>Taken together, these data suggest that NT enhances DA release principally by inhibiting the function of terminal D<sub>2 </sub>autoreceptors and not by more direct mechanisms such as facilitation of terminal calcium influx.</p> |
| first_indexed | 2024-12-20T00:21:40Z |
| format | Article |
| id | doaj.art-f9a8a29aa3e249cfada8448d4319d892 |
| institution | Directory Open Access Journal |
| issn | 1471-2202 |
| language | English |
| last_indexed | 2024-12-20T00:21:40Z |
| publishDate | 2009-08-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Neuroscience |
| spelling | doaj.art-f9a8a29aa3e249cfada8448d4319d8922022-12-21T20:00:10ZengBMCBMC Neuroscience1471-22022009-08-011019610.1186/1471-2202-10-96Presynaptic action of neurotensin on dopamine release through inhibition of D<sub>2 </sub>receptor functionTrudeau Louis-EricLeo DamianaMartel PhilippeFawaz Charbel S<p>Abstract</p> <p>Background</p> <p>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).</p> <p>Results</p> <p>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<sub>2 </sub>autoreceptors and the presynaptic action of NT in the NAcc shell and shell/core border region. The selective agonist of D<sub>2 </sub>autoreceptors, quinpirole (1 μM), inhibited DA overflow evoked by both single and train pulses. In sharp contrast, the selective D<sub>2 </sub>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<sub>2 </sub>autoreceptors. In addition, initial blockade of D<sub>2 </sub>autoreceptors by sulpiride considerably inhibited further facilitation of DA release generated by NT (8–13).</p> <p>Conclusion</p> <p>Taken together, these data suggest that NT enhances DA release principally by inhibiting the function of terminal D<sub>2 </sub>autoreceptors and not by more direct mechanisms such as facilitation of terminal calcium influx.</p>http://www.biomedcentral.com/1471-2202/10/96 |
| spellingShingle | Trudeau Louis-Eric Leo Damiana Martel Philippe Fawaz Charbel S Presynaptic action of neurotensin on dopamine release through inhibition of D<sub>2 </sub>receptor function BMC Neuroscience |
| title | Presynaptic action of neurotensin on dopamine release through inhibition of D<sub>2 </sub>receptor function |
| title_full | Presynaptic action of neurotensin on dopamine release through inhibition of D<sub>2 </sub>receptor function |
| title_fullStr | Presynaptic action of neurotensin on dopamine release through inhibition of D<sub>2 </sub>receptor function |
| title_full_unstemmed | Presynaptic action of neurotensin on dopamine release through inhibition of D<sub>2 </sub>receptor function |
| title_short | Presynaptic action of neurotensin on dopamine release through inhibition of D<sub>2 </sub>receptor function |
| title_sort | presynaptic action of neurotensin on dopamine release through inhibition of d sub 2 sub receptor function |
| url | http://www.biomedcentral.com/1471-2202/10/96 |
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