The role of tissue plasminogen activator in methamphetamine‐related reward and sensitization

Nagai, Taku; Noda, Yukihiro; Ishikawa, Kazuhiro; Miyamoto, Yukio; Yoshimura, Masako; Ito, Makoto; Takayanagi, Masanori; Takuma, Kazuhiro; Yamada, Kiyofumi; Nabeshima, Toshitaka

doi:10.1111/j.1471-4159.2004.02903.x

Cited by 54 publications

(68 citation statements)

References 57 publications

(100 reference statements)

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“…The effect of repeated methamphetamine treatment on tPA mRNA expression in the NAc was dose-dependent and was completely blocked by pretreatment with either the dopamine D1 receptor antagonist R(+)-SCH23390 or dopamine-D2-receptor antagonist reclopride. We confirmed that repeated methamphetamine treatment significantly increased tPA activity in the NAc compared with the saline-treated group, although single methamphetamine treatment had no effect (32). On the other hand, Hashimoto et al (33) demonstrated that a single injection of psychostimulants, including methamphetamine, cocaine, and phencyclidine, induced tPA mRNA expression in the medial and insular prefrontal cortex and the piriform cortex using in situ hybridization histochemistry.…”

Section: A Role For Tpa In Methamphetamine Dependencesupporting

confidence: 61%

Drug Dependence, Synaptic Plasticity, and Tissue Plasminogen Activator

2005

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Abstract. The mesocorticolimbic dopaminergic system plays an important role in the reinforcing effects of drugs of abuse, and the activity-dependent synaptic plasticity of the system is involved in drug dependence. A DNA microarray screening revealed that the expression levels of tissue plasminogen activator (tPA) mRNA in the nucleus accumbens of morphine-or methamphetamine-dependent rats were significantly increased compared with those in control animals. Since tPA plays a role in synaptic plasticity, we hypothesized that tPA may contribute to the development of drug dependence. Single and repeated morphine treatment as well as repeated methamphetamine treatment induced tPA mRNA expression in the nucleus accumbens, which was associated with an increase in the enzyme activity. Conditioned place preference induced by morphine was markedly reduced in mice with a targeted deletion of the tPA gene (tPA-/ -mice), being accompanied by a loss of morphine-induced dopamine release. Similarly, methamphetamine-induced conditioned place preference and locomotor sensitization were reduced in tPA-/ -mice. The defects of morphine-induced hyperlocomotion as well as methamphetamineinduced locomotor sensitization in tPA-/ -mice were reversed by microinjection of exogenous tPA or plasmin into the nucleus accumbens. These results support our hypothesis that tPA plays a role in long-lasting neuronal changes related to drug dependence.

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Section: A Role For Tpa In Methamphetamine Dependencesupporting

confidence: 61%

Drug Dependence, Synaptic Plasticity, and Tissue Plasminogen Activator

2005

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“…Pharmacologic inhibition of tPA in the NAc reduces morphineinduced dopamine release (Nagai et al, 2005b). We also demonstrated that tPA is involved in the rewarding effect of methamphetamine (Nagai et al, 2005a). These findings suggest that the tPA-plasmin system amplifies the rewarding effects of drugs of abuse, by regulating dopamine release in the NAc (Yamada et al, 2005).…”

Section: Introductionmentioning

confidence: 66%

The Rewards of Nicotine: Regulation by Tissue Plasminogen Activator–Plasmin System through Protease Activated Receptor-1

Nagai

Ito²,

Nakamichi³

et al. 2006

J. Neurosci.

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Nicotine, a primary component of tobacco, is one of the most abused drugs worldwide. Approximately four million people die each year because of diseases associated with tobacco smoking. Mesolimbic dopaminergic neurons mediate the rewarding effects of abused drugs, including nicotine. Here we show that the tissue plasminogen activator (tPA)-plasmin system regulates nicotine-induced reward and dopamine release by activating protease activated receptor-1 (PAR1). In vivo microdialysis revealed that microinjection of either tPA or plasmin into the nucleus accumbens (NAc) significantly potentiated whereas plasminogen activator inhibitor-1 reduced the nicotineinduced dopamine release in the NAc in a dose-dependent manner. Nicotine-induced dopamine release was markedly diminished in tPA-deficient (tPA Ϫ/Ϫ )mice, and the defect of dopamine release in tPA Ϫ/Ϫ mice was restored by microinjection of either exogenous tPA or plasmin into the NAc. Nicotine increased tPA protein levels and promoted the release of tPA into the extracellular space in the NAc. Immunohistochemistry revealed that PAR1 immunoreactivity was localized to the nerve terminals positive for tyrosine hydroxylase in the NAc. Furthermore, we demonstrated that plasmin activated PAR1 and that nicotine-induced place preference and dopamine release were diminished in PAR1-deficient (PAR1 Ϫ/Ϫ ) mice. Targeting the tPA-plasmin-PAR1 system would provide new therapeutic approaches to the treatment of nicotine dependence.

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“…The present study firmly consolidates these data and points to an important role of the plasmin system in chronic cocaine. Other studies have shown that the plasmin system releases dopamine in the NAc upon psychostimulants, which activates long-term synaptic plasticity and remodeling, and acutely participates in the rewarding effects of drugs such as methamphetamine or morphine [13,14,16,17,69]. It has been shown that tPA regulates nicotine-induced reward and dopamine release through protease activated receptor-1 [70].…”

Section: Discussionmentioning

confidence: 99%

Effects of urokinase-type plasminogen activator in the acquisition, expression and reinstatement of cocaine-induced conditioned-place preference

Bahí

Kusnecov

Dreyer

2008

Behavioural Brain Research

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a b s t r a c tCocaine and many other psychostimulants strongly induce urokinase-type plasminogen activator (uPA) expression in the mesolimbic dopaminergic pathway, which plays a major role in drug-mediated behavioral plasticity [Bahi A, Boyer F, Gumy C, Kafri T, Dreyer JL. In vivo gene delivery of urokinase-type plasminogen activator with regulatable lentivirus induces behavioral changes in chronic cocaine administration. Eur J Neurosci 2004;20:3473-88; Bahi A, Boyer F, Kafri T, Dreyer JL. Silencing urokinase in the ventral tegmental area in vivo induces changes in cocaine-induced hyperlocomotion. J Neurochem 2006;98:1619-31; Bahi A, Dreyer JL. Overexpression of plasminogen activators in the nucleus accumbens enhances cocaine-, amphetamine-and morphine-induced reward and behavioral sensitization. Genes Brain Behav 2007]. In this study, the role of mesolimbic dopamine (DA) pathways in the development of cocaine reward was examined by conditioned-place preference in rats with bilateral intra-accumbens injections of uPA-expressing lentiviral vectors. We show that overexpression of uPA in the Nac significantly augments cocaine-induced place preference. Furthermore, while this did not affect the ability of preference to be extinguished, reinstatement with a low dose of cocaine produced significantly greater preference to the cocaine-associated context. Once CPP had been established, and the preference extinguished, reinstatement induced by a priming dose of cocaine was facilitated by uPA. Inhibition of this serine protease expression using doxycycline abolished the augmented acquisition produced by overexpression of uPA but not the expression of the cocaine-induced CPP. When uPA is inhibited during the acquisition phase, animals no longer demonstrate place preference for the environment previously paired with cocaine. B428, a specific uPA inhibitor does not affect drug reinstatement after extinction if uPA has been activated during acquisition, a clear indication that uPA is involved in the acquisition phase of conditioned-place preference. Our results suggest that that increased uPA expression with repeated drug exposure produces conditions for enhanced acquisition of cocaine-induced CPP, indicating that cocaine-induced CPP and reinstatement may be dependent on active extracellular uPA.

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The role of tissue plasminogen activator in methamphetamine‐related reward and sensitization

Cited by 54 publications

References 57 publications

Drug Dependence, Synaptic Plasticity, and Tissue Plasminogen Activator

Drug Dependence, Synaptic Plasticity, and Tissue Plasminogen Activator

The Rewards of Nicotine: Regulation by Tissue Plasminogen Activator–Plasmin System through Protease Activated Receptor-1

Effects of urokinase-type plasminogen activator in the acquisition, expression and reinstatement of cocaine-induced conditioned-place preference

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