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ToolsNavarro, Gemma, Moreno, Estefanía, Aymerich, Marisol, Marcellino, Daniel, McCormick, Peter J., Mallol, Josefa, Cortés, Antoni, Casadó, Vicent, Canela, Enric I., Ortiz, Jordi, Fuxe, Kjell, Lluís, Carmen, Ferré, Sergi and Franco, Rafael (2010) Direct involvement of σ-1 receptors in the dopamine D receptor-mediated effects of cocaine. Proceedings of the National Academy of Sciences of the United States of America (PNAS), 107 (43). pp. 18676-18681. ISSN 0027-8424
Full text not available from this repository.Abstract
It is well known that cocaine blocks the dopamine transporter. This mechanism should lead to a general increase in dopaminergic neurotransmission, and yet dopamine D receptors (DRs) playamore significant role in the behavioral effects of cocaine than the other dopamine receptor subtypes. Cocaine also binds to σ-1 receptors, the physiological role of which is largely unknown. In the present study, DR and σR were found to heteromerize in transfected cells, where cocaine robustly potentiated DR-mediated adenylyl cyclase activation, induced MAPK activation per se and counteracted MAPK activation induced by DR stimulation in a dopamine transporter-independent and σR-dependent manner. Some of these effects were also demonstrated in murine striatal slices and were absent in σR KO mice, providing evidence for the existence of σR-D R heteromers in the brain. Therefore, these results provide a molecular explanation for which DR playsamore significant role in the behavioral effects of cocaine, through σR-DR heteromerization, and provide a unique perspective toward understanding the molecular basis of cocaine addiction.
| Item Type: | Article |
|---|---|
| Faculty \ School: | Faculty of Science > School of Pharmacy |
| Related URLs: | |
| Depositing User: | Pure Connector |
| Date Deposited: | 13 Jan 2014 13:28 |
| Last Modified: | 24 Oct 2022 05:57 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/47157 |
| DOI: | 10.1073/pnas.1008911107 |
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