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Modification by the tissue plasminogen activator–plasmin system of morphine‐induced dopamine release and hyperlocomotion, but not anti‐nociceptive effect in mice
Author(s) -
Nagai Taku,
Kamei Hiroyuki,
Ito Mina,
Hashimoto Kazuki,
Takuma Kazuhiro,
Nabeshima Toshitaka,
Yamada Kiyofumi
Publication year - 2005
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2005.03117.x
Subject(s) - morphine , dopamine , plasmin , microinjection , chemistry , nociception , tissue plasminogen activator , nucleus accumbens , pharmacology , plasminogen activator , endocrinology , medicine , biochemistry , receptor , enzyme
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.