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Activation of post‐synaptic dopamine D 1 receptors promotes the release of tissue plasminogen activator in the nucleus accumbens via PKA signaling
Author(s) -
Ito Mina,
Nagai Taku,
Mizoguchi Hiroyuki,
Sato Kosuke,
Hayase Minoru,
Otsuka Noboru,
Fukakusa Ayumi,
Kumagai Nozomi,
Kim HyoungChun,
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.1471-4159.2007.04946.x
Subject(s) - dopamine , chemistry , agonist , nucleus accumbens , pharmacology , quinpirole , raclopride , dopamine receptor d1 , dopamine receptor d2 , medicine , endocrinology , receptor , biology , biochemistry
We have previously demonstrated that tissue plasminogen activator (tPA) plays an important role through the conversion of plasminogen to plasmin in the release of dopamine in the nucleus accumbens (NAc) evoked by depolarization or the systemic administration of drugs of abuse such as morphine and nicotine. In the present study, we examined the mechanisms by which drugs of abuse increase extracellular tPA activity in the NAc in vivo using in situ zymography. The dopamine D 1 receptor (D 1 R) agonist SKF38393, but not D 2 receptor agonist quinpirole, significantly increased extracellular tPA activity in the NAc. The effect of SKF38393 was blocked by pre‐treatment with the dopamine D 1 R antagonist SCH23390. Microinjection of Rp‐cAMPs, a protein kinase A inhibitor, into the NAc completely blocked the effect of SKF38393. Systemic administration of morphine and methamphetamine increased extracellular tPA activity in the NAc, and these effects were completely blocked by pre‐treatment with SCH23390 and raclopride. The results suggest that activation of post‐synaptic dopamine D 1 Rs in the NAc leads to an increase in extracellular tPA activity via protein kinase A signaling. Furthermore, dopamine D 2 receptors are also involved in the release of tPA induced by morphine and methamphetamine.