Possible involvement of protease-activated receptor-1 in the regulation of morphine-induced dopamine release and hyperlocomotion by the tissue plasminogen activator-plasmin system.
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.
Ito
Mina
M
Laboratory of Neuropsychopharmacology, Division of Life Sciences, Graduate School of Natural Science and Technology, Kanazawa University, Kanazawa, Japan.
Nagai
Taku
T
Mizoguchi
Hiroyuki
H
Fukakusa
Ayumi
A
Nakanishi
Yutaka
Y
Kamei
Hiroyuki
H
Nabeshima
Toshitaka
T
Takuma
Kazuhiro
K
Yamada
Kiyofumi
K
D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D006948:Hyperkinesis / Q000139:chemically induced / Q000378:metabolism*; D017403:In Situ Hybridization / Q000379:methods; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009020:Morphine / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000187:drug effects; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044463:Receptor, PAR-1 / Q000172:deficiency / Q000502:physiology*; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000378:metabolism*; D010975:Platelet Aggregation Inhibitors
D009292:Narcotic Antagonists; D009294:Narcotics; D010446:Peptide Fragments; D044463:Receptor, PAR-1; C086309:thrombin receptor peptide SFLLRNP; D009270:Naloxone; D009020:Morphine; D010959:Tissue Plasminogen Activator; D004298:Dopamine; D010975:Platelet Aggregation Inhibitors