Modification by the tissue plasminogen activator-plasmin system of morphine-induced dopamine release and hyperlocomotion, but not anti-nociceptive effect in mice

Taku Nagai, Hiroyuki Kamei, Mina Ito, Kazuki Hashimoto, Kazuhiro Takuma, Toshitaka Nabeshima, Kiyofumi Yamada

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

The extracellular serine protease tissue plasminogen activator (tPA) that converts plasminogen into plasmin is abundantly expressed throughout the central nervous system. We have recently demonstrated that the tPA-plasmin system participates in the rewarding and locomotor-stimulating effects of morphine by acutely regulating morphine-induced dopamine release in the nucleus accumbens (NAc). In the present study, we examined the effects of microinjections of plasminogen activator inhibitor-1 (PAI-1), tPA or plasmin into the NAc on morphine-induced dopamine release, hyperlocomotion and anti-nociceptive effects in ICR mice. A single morphine treatment resulted in an increase in protein levels of PAI-1 in the NAc. Microinjection of PAI-1 into the NAc dose-dependently reduced morphine-induced dopamine release and hyperlocomotion. In contrast, microinjection of tPA into the NAc significantly potentiated morphine-induced dopamine release and hyperlocomotion without affecting basal levels. Furthermore, microinjection of plasmin enhanced morphine-induced dopamine release, but did not modify the hyperlocomotion induced by morphine. The intracerebroventricular injection of PAI-1, tPA and plasmin at high doses had no effect on the anti-nociceptive effects of morphine. These results suggest that the tPA-plasmin system is involved in the regulation of morphine-induced dopamine release and dopamine-dependent behaviors but not the anti-nociceptive effects of morphine.

Original languageEnglish
Pages (from-to)1272-1279
Number of pages8
JournalJournal of Neurochemistry
Volume93
Issue number5
DOIs
Publication statusPublished - 01-06-2005
Externally publishedYes

    Fingerprint

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this