| First Author | Navarro G | Year | 2010 |
| Journal | Proc Natl Acad Sci U S A | Volume | 107 |
| Issue | 43 | Pages | 18676-81 |
| PubMed ID | 20956312 | Mgi Jnum | J:165484 |
| Mgi Id | MGI:4837560 | Doi | 10.1073/pnas.1008911107 |
| Citation | Navarro G, et al. (2010) Direct involvement of sigma-1 receptors in the dopamine D1 receptor-mediated effects of cocaine. Proc Natl Acad Sci U S A 107(43):18676-81 |
| abstractText | 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(1) receptors (D(1)Rs) play a more significant role in the behavioral effects of cocaine than the other dopamine receptor subtypes. Cocaine also binds to sigma-1 receptors, the physiological role of which is largely unknown. In the present study, D(1)R and sigma(1)R were found to heteromerize in transfected cells, where cocaine robustly potentiated D(1)R-mediated adenylyl cyclase activation, induced MAPK activation per se and counteracted MAPK activation induced by D(1)R stimulation in a dopamine transporter-independent and sigma(1)R-dependent manner. Some of these effects were also demonstrated in murine striatal slices and were absent in sigma(1)R KO mice, providing evidence for the existence of sigma(1)R-D(1)R heteromers in the brain. Therefore, these results provide a molecular explanation for which D(1)R plays a more significant role in the behavioral effects of cocaine, through sigma(1)R-D(1)R heteromerization, and provide a unique perspective toward understanding the molecular basis of cocaine addiction. |
