In heterozygous GDNF knockout mice the response of striatal dopaminergic system to acute morphine is altered

Mikko Airavaara, Jelena Mijatovic, Tanja Vihavainen, Petteri Piepponen, Mart Saarma, Liisa Ahtee

    Research output: Contribution to journalArticleScientificpeer-review

    Abstract

    Glial cell line-derived neurotrophic factor (GDNF) regulates striatal dopaminergic neurons. To study whether reduced endogenous GDNF affect morphine's effects on striatal dopamine transmission, we estimated extracellular concentrations of dopamine and its metabolites by microdialysis in vivo and tissue concentrations post mortem in mice lacking one GDNF allele (GDNF+/- mice). In the wild-type mice, acute morphine (5 and 10 mg/kg s.c.) increased accumbal dopamine output dose-dependently (maximally by 30 and 80%, respectively). In the GDNF+/- mice, 5 mg/kg of morphine enhanced the accumbal dopamine output maximally by 11.0%, and significantly more than morphine 10 mg/kg (maximally by 60%). Also, the response of extracellular accumbal DOPAC to acute morphine was significantly altered in the GDNF+/- mice. In mice of both genotypes, the responses to morphine in the caudate putamen were similar to but much less intense than those in the nucleus accumbens. Morphine at the doses 5, 10, and 30 mg/kg dose-dependently elevated the striatal tissue concentrations of DOPAC and HVA, but the effect of 30 mg/kg was significantly smaller in the GDNF+/- mice than in their wild-type littermates. The binding of [H-3]DAMGO to striatal membrane homogenates was similar between the genotypes. However, morphine induced antinociception in the GDNF+/- mice at a smaller dose than in the controls. The finding that reduced GDNF level alters the effects of morphine on striatal dopamine and our previous findings of elevated extracellular striatal dopamine concentrations and FosB/Delta FosB expression in the GDNF+/- mice show the importance of GDNF in the regulation of striatal dopaminergic system.
    Original languageEnglish
    JournalSynapse (New York)
    Volume59
    Issue number6
    Pages (from-to)321-329
    Number of pages9
    ISSN0887-4476
    DOIs
    Publication statusPublished - 2006
    MoE publication typeA1 Journal article-refereed

    Cite this

    @article{c07b012234de4ab1b212e6f83720a8b9,
    title = "In heterozygous GDNF knockout mice the response of striatal dopaminergic system to acute morphine is altered",
    abstract = "Glial cell line-derived neurotrophic factor (GDNF) regulates striatal dopaminergic neurons. To study whether reduced endogenous GDNF affect morphine's effects on striatal dopamine transmission, we estimated extracellular concentrations of dopamine and its metabolites by microdialysis in vivo and tissue concentrations post mortem in mice lacking one GDNF allele (GDNF+/- mice). In the wild-type mice, acute morphine (5 and 10 mg/kg s.c.) increased accumbal dopamine output dose-dependently (maximally by 30 and 80{\%}, respectively). In the GDNF+/- mice, 5 mg/kg of morphine enhanced the accumbal dopamine output maximally by 11.0{\%}, and significantly more than morphine 10 mg/kg (maximally by 60{\%}). Also, the response of extracellular accumbal DOPAC to acute morphine was significantly altered in the GDNF+/- mice. In mice of both genotypes, the responses to morphine in the caudate putamen were similar to but much less intense than those in the nucleus accumbens. Morphine at the doses 5, 10, and 30 mg/kg dose-dependently elevated the striatal tissue concentrations of DOPAC and HVA, but the effect of 30 mg/kg was significantly smaller in the GDNF+/- mice than in their wild-type littermates. The binding of [H-3]DAMGO to striatal membrane homogenates was similar between the genotypes. However, morphine induced antinociception in the GDNF+/- mice at a smaller dose than in the controls. The finding that reduced GDNF level alters the effects of morphine on striatal dopamine and our previous findings of elevated extracellular striatal dopamine concentrations and FosB/Delta FosB expression in the GDNF+/- mice show the importance of GDNF in the regulation of striatal dopaminergic system.",
    author = "Mikko Airavaara and Jelena Mijatovic and Tanja Vihavainen and Petteri Piepponen and Mart Saarma and Liisa Ahtee",
    year = "2006",
    doi = "10.1002/syn.20245",
    language = "English",
    volume = "59",
    pages = "321--329",
    journal = "Synapse (New York)",
    issn = "0887-4476",
    publisher = "John Wiley & Sons Ltd.",
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    In heterozygous GDNF knockout mice the response of striatal dopaminergic system to acute morphine is altered. / Airavaara, Mikko; Mijatovic, Jelena; Vihavainen, Tanja; Piepponen, Petteri; Saarma, Mart; Ahtee, Liisa.

    In: Synapse (New York), Vol. 59, No. 6, 2006, p. 321-329.

    Research output: Contribution to journalArticleScientificpeer-review

    TY - JOUR

    T1 - In heterozygous GDNF knockout mice the response of striatal dopaminergic system to acute morphine is altered

    AU - Airavaara, Mikko

    AU - Mijatovic, Jelena

    AU - Vihavainen, Tanja

    AU - Piepponen, Petteri

    AU - Saarma, Mart

    AU - Ahtee, Liisa

    PY - 2006

    Y1 - 2006

    N2 - Glial cell line-derived neurotrophic factor (GDNF) regulates striatal dopaminergic neurons. To study whether reduced endogenous GDNF affect morphine's effects on striatal dopamine transmission, we estimated extracellular concentrations of dopamine and its metabolites by microdialysis in vivo and tissue concentrations post mortem in mice lacking one GDNF allele (GDNF+/- mice). In the wild-type mice, acute morphine (5 and 10 mg/kg s.c.) increased accumbal dopamine output dose-dependently (maximally by 30 and 80%, respectively). In the GDNF+/- mice, 5 mg/kg of morphine enhanced the accumbal dopamine output maximally by 11.0%, and significantly more than morphine 10 mg/kg (maximally by 60%). Also, the response of extracellular accumbal DOPAC to acute morphine was significantly altered in the GDNF+/- mice. In mice of both genotypes, the responses to morphine in the caudate putamen were similar to but much less intense than those in the nucleus accumbens. Morphine at the doses 5, 10, and 30 mg/kg dose-dependently elevated the striatal tissue concentrations of DOPAC and HVA, but the effect of 30 mg/kg was significantly smaller in the GDNF+/- mice than in their wild-type littermates. The binding of [H-3]DAMGO to striatal membrane homogenates was similar between the genotypes. However, morphine induced antinociception in the GDNF+/- mice at a smaller dose than in the controls. The finding that reduced GDNF level alters the effects of morphine on striatal dopamine and our previous findings of elevated extracellular striatal dopamine concentrations and FosB/Delta FosB expression in the GDNF+/- mice show the importance of GDNF in the regulation of striatal dopaminergic system.

    AB - Glial cell line-derived neurotrophic factor (GDNF) regulates striatal dopaminergic neurons. To study whether reduced endogenous GDNF affect morphine's effects on striatal dopamine transmission, we estimated extracellular concentrations of dopamine and its metabolites by microdialysis in vivo and tissue concentrations post mortem in mice lacking one GDNF allele (GDNF+/- mice). In the wild-type mice, acute morphine (5 and 10 mg/kg s.c.) increased accumbal dopamine output dose-dependently (maximally by 30 and 80%, respectively). In the GDNF+/- mice, 5 mg/kg of morphine enhanced the accumbal dopamine output maximally by 11.0%, and significantly more than morphine 10 mg/kg (maximally by 60%). Also, the response of extracellular accumbal DOPAC to acute morphine was significantly altered in the GDNF+/- mice. In mice of both genotypes, the responses to morphine in the caudate putamen were similar to but much less intense than those in the nucleus accumbens. Morphine at the doses 5, 10, and 30 mg/kg dose-dependently elevated the striatal tissue concentrations of DOPAC and HVA, but the effect of 30 mg/kg was significantly smaller in the GDNF+/- mice than in their wild-type littermates. The binding of [H-3]DAMGO to striatal membrane homogenates was similar between the genotypes. However, morphine induced antinociception in the GDNF+/- mice at a smaller dose than in the controls. The finding that reduced GDNF level alters the effects of morphine on striatal dopamine and our previous findings of elevated extracellular striatal dopamine concentrations and FosB/Delta FosB expression in the GDNF+/- mice show the importance of GDNF in the regulation of striatal dopaminergic system.

    U2 - 10.1002/syn.20245

    DO - 10.1002/syn.20245

    M3 - Article

    VL - 59

    SP - 321

    EP - 329

    JO - Synapse (New York)

    JF - Synapse (New York)

    SN - 0887-4476

    IS - 6

    ER -