| First Author | Ito M | Year | 2007 |
| Journal | J Neurochem | Volume | 101 |
| Issue | 5 | Pages | 1392-9 |
| PubMed ID | 17286591 | Mgi Jnum | J:122545 |
| Mgi Id | MGI:3714664 | Doi | 10.1111/j.1471-4159.2006.04423.x |
| Citation | Ito M, et al. (2007) Possible involvement of protease-activated receptor-1 in the regulation of morphine-induced dopamine release and hyperlocomotion by the tissue plasminogen activator-plasmin system. J Neurochem 101(5):1392-9 |
| abstractText | We have previously demonstrated that tissue plasminogen activator (tPA)-plasmin system participates in the rewarding effect of morphine, by regulating dopamine release in the nucleus accumbens (NAc). However, it is unclear how plasmin increases the morphine-induced release of dopamine and hyperlocomotion. In the present study we investigated whether protease activated receptor-1 (PAR-1) is involved in the regulation of acute morphine-induced dopamine release by the tPA-plasmin system. Morphine significantly but transiently increased extracellular tPA activity in the NAc, which was completely blocked by naloxone. Microinjection of a PAR-1 antagonist, (tyr(-1))-thrombin receptor activating peptide 7, into the NAc significantly reduced morphine-induced dopamine release in the NAc and hyperlocomotion although the treatment had no effect on basal dopamine release and spontaneous locomotor activity. Furthermore, the PAR-1 antagonist blocked the ameliorating effect of plasmin on the defect of morphine-induced dopamine release in the NAc of tPA-deficient mice. In contrast, intracerebroventricular injection of the PAR-1 antagonist had no effect on the antinociceptive effects of morphine in mice. These results suggest that PAR-1 is a target for the tPA-plasmin system in the regulation of acute morphine-induced dopamine release in the NAc. |
