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Possible involvement of protease‐activated receptor‐1 in the regulation of morphine‐induced dopamine release and hyperlocomotion by the tissue plasminogen activator‐plasmin system
Author(s) -
Ito Mina,
Nagai Taku,
Mizoguchi Hiroyuki,
Fukakusa Ayumi,
Nakanishi Yutaka,
Kamei Hiroyuki,
Nabeshima Toshitaka,
Takuma Kazuhiro,
Yamada Kiyofumi
Publication year - 2007
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.1471-4159.2006.04423.x
Subject(s) - dopamine , plasmin , chemistry , morphine , nucleus accumbens , pharmacology , tissue plasminogen activator , receptor antagonist , (+) naloxone , receptor , endocrinology , medicine , antagonist , biology , biochemistry , enzyme
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.