| First Author | Nagai T | Year | 2004 |
| Journal | Proc Natl Acad Sci U S A | Volume | 101 |
| Issue | 10 | Pages | 3650-5 |
| PubMed ID | 14988509 | Mgi Jnum | J:88913 |
| Mgi Id | MGI:3037419 | Doi | 10.1073/pnas.0306587101 |
| Citation | Nagai T, et al. (2004) The tissue plasminogen activator-plasmin system participates in the rewarding effect of morphine by regulating dopamine release. Proc Natl Acad Sci U S A 101(10):3650-5 |
| abstractText | Tissue plasminogen activator (tPA) is a serine protease that catalyzes the conversion of plasminogen (plg) to plasmin, which in turn functions to degrade extracellular matrix proteins in the central nervous system. The tPA-plasmin system plays a role in synaptic plasticity and remodeling. Here we show that this protease system participates in the rewarding effects of morphine by acutely regulating morphine-induced dopamine release in the nucleus accumbens (NAcc). A single morphine treatment induced tPA mRNA and protein expression in a naloxone-sensitive manner, which was associated with an increase in the enzyme activity in the NAcc. The acute effect of morphine in inducing tPA expression was diminished after repeated administration. Morphine-induced conditioned place preference and hyperlocomotion were significantly reduced in tPA(-/-) and plg(-/-) mice, being accompanied by a loss of morphine-induced dopamine release in the NAcc. The defect of morphine-induced dopamine release and hyperlocomotion in tPA(-/-) mice was reversed by microinjections of either exogenous tPA or plasmin into the NAcc. Our findings demonstrate a previously undescribed function of the tPA-plasmin system in regulating dopamine release, which is involved in the rewarding effects of morphine. |
