Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 2589-2596 |
| Number of pages | 8 |
| Journal | Journal of neurochemistry |
| Volume | 103 |
| Issue number | 6 |
| Publication status | Published - 01-12-2007 |
| Externally published | Yes |
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All Science Journal Classification (ASJC) codes
- Biochemistry
- Cellular and Molecular Neuroscience
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Activation of post-synaptic dopamine D receptors promotes the release of tissue plasminogen activator in the nucleus accumbens via PKA signaling. / Ito, Mina; Nagai, Taku; Mizoguchi, Hiroyuki; Sato, Kosuke; Hayase, Minoru; Otsuka, Noboru; Fukakusa, Ayumi; Kumagai, Nozomi; Kim, Hyoung Chun; Nabeshima, Toshitaka; Takuma, Kazuhiro; Yamada, Kiyofumi.
In: Journal of neurochemistry, Vol. 103, No. 6, 01.12.2007, p. 2589-2596.Research output: Contribution to journal › Article
TY - JOUR
T1 - Activation of post-synaptic dopamine D receptors promotes the release of tissue plasminogen activator in the nucleus accumbens via PKA signaling.
AU - Ito, Mina
AU - Nagai, Taku
AU - Mizoguchi, Hiroyuki
AU - Sato, Kosuke
AU - Hayase, Minoru
AU - Otsuka, Noboru
AU - Fukakusa, Ayumi
AU - Kumagai, Nozomi
AU - Kim, Hyoung Chun
AU - Nabeshima, Toshitaka
AU - Takuma, Kazuhiro
AU - Yamada, Kiyofumi
PY - 2007/12/1
Y1 - 2007/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=40949091521&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=40949091521&partnerID=8YFLogxK
M3 - Article
C2 - 17944865
AN - SCOPUS:40949091521
VL - 103
SP - 2589
EP - 2596
JO - Journal of Neurochemistry
JF - Journal of Neurochemistry
SN - 0022-3042
IS - 6
ER -