2006
DOI: 10.1124/mol.106.022467
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Involvement of Tissue Plasminogen Activator-Plasmin System in Depolarization-Evoked Dopamine Release in the Nucleus Accumbens of Mice

Abstract: Tissue plasminogen activator (tPA), a serine protease, catalyzes the conversion of plasminogen to plasmin. In the present study, we investigated the role of the tPA-plasmin system in depolarization-evoked dopamine (DA) and acetylcholine (ACh) release in the nucleus accumbens (NAc) and hippocampus, respectively, of mice, by using in vivo microdialysis. Microinjection of either tPA or plasmin significantly potentiated 40 mM KCl-induced DA release without affecting basal DA levels. In contrast, plasminogen activa… Show more

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Cited by 24 publications
(21 citation statements)
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“…In addition, we recently demonstrated that administration of therapeutically relevant concentrations of rt-PA to guinea pig heart synaptosomes and primary cultures of human neuroblastoma SH-SY5Y cells releases NE as a function of its concentration (Schaefer et al, 2006). In agreement with our findings, a recent study demonstrated that the release of dopamine and acetylcholine evoked by depolarization in mouse brain was markedly enhanced by local rt-PA microinjections, whereas it was reduced by PAI-1 administration and in t-PA Ϫ/Ϫ mice (Ito et al, 2006). We postulate that the activity level of t-PA will determine the magnitude of NE release.…”
Section: Discussionsupporting
confidence: 81%
“…In addition, we recently demonstrated that administration of therapeutically relevant concentrations of rt-PA to guinea pig heart synaptosomes and primary cultures of human neuroblastoma SH-SY5Y cells releases NE as a function of its concentration (Schaefer et al, 2006). In agreement with our findings, a recent study demonstrated that the release of dopamine and acetylcholine evoked by depolarization in mouse brain was markedly enhanced by local rt-PA microinjections, whereas it was reduced by PAI-1 administration and in t-PA Ϫ/Ϫ mice (Ito et al, 2006). We postulate that the activity level of t-PA will determine the magnitude of NE release.…”
Section: Discussionsupporting
confidence: 81%
“…Microinjection of tPA or plasmin into the NAc dramatically increased morphine-induced dopamine release in tPA−/− mice, as observed in wild-type mice, although microinjection of tPA into the VTA had no effect on morphine-induced dopamine release in the NAc of tPA−/ − mice (11). In addition, microinjections of either exogenous tPA or plasmin into the NAc of tPA−/ − mice restored the defect of high-potassium-evoked dopamine release in the NAc of the mutant mice (9). It is plausible that plasmin converted from plg by tPA may have a role in the regulation of dopamine release in the NAc.…”
Section: Regulation Of Nicotine-induced Dopamine and Ach Release By Tmentioning
confidence: 78%
“…Moreover, as previously mentioned, the tPA-plasmin system is involved in the rewarding effects of drugs of abuse (eg, morphine), possibly through regulation of dopamine release in the NAc (Nagai et al, 2004Ito et al, 2006Ito et al, , 2007Yan et al, 2007). Indeed, similar to the present findings involving the use of LV-siRNA, tPA-knockout mice showed a reduction in morphine-, methamphetamine-, and nicotine-induced CPP and locomotor sensitization (Nagai et al, 2004Ito et al, 2006Ito et al, , 2007Yan et al, 2007). Furthermore, exogenous recombinant human tPA or plasmin restored the defect of morphine-induced dopamine release in the NAc and hyperactivity in tPA-knockout mice (Nagai et al, 2004).…”
Section: Discussionmentioning
confidence: 99%