title: Methamphetamine-sensitized rats show augmented dopamine release to methylphenidate stimulation: a positron emission tomography using [18F]fallypride.
abstract: Previous studies demonstrated that patients with schizophrenia show greater sensitivity to psychostimulants than healthy subjects. Sensitization to psychostimulants and resultant alteration of dopaminergic neurotransmission in rodents have been suggested as a useful model of schizophrenia. This study was aimed to examine the use of methylphenidate as a psychostimulant to induce dopamine release and that of [18F]fallypride as a radioligand to estimate the release in a rat model of schizophrenia. Six rats were scanned by positron emission tomography (PET) twice before and after methylphenidate challenge to evaluate dopamine release. After the scans, these rats were sensitized by using repeated methamphetamine (MAP) administration. Then, they were re-scanned twice again before and after methylphenidate challenge to evaluate whether MAP-sensitized rats show greater sensitivity to methylphenidate. We revealed a main effect of MAP-pretreatment and that of metylphenidate challenge. We found that % change of distribution volume ratio after repeated administration of MAP was greater than that before sensitization. These results suggest that methylphenidate-induced striatal dopamine release increased after sensitization to MAP. PET scan using [18F]fallypride at methylphenidate-challenge may provide a biological marker for schizophrenia and be useful to diagnose schizophrenia.
authors.affiliation: Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry4-1-1 Ogawa-Higashi, KodairaTokyo187-8502, Japan. Electronic address: ota@ncnp.go.jp.
authors.forename: Miho
authors.initials: M
authors.lastname: Ota
authors.affiliation: Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry4-1-1 Ogawa-Higashi, KodairaTokyo187-8502, Japan.
authors.forename: Shintaro
authors.initials: S
authors.lastname: Ogawa
authors.affiliation: Organic Radiochemistry Section, Department of Advanced Neuroimaging, Integrative Brain Imaging Center, National Center Hospital of Neurology and Psychiatry, 4-1-1 Ogawa-Higashi, Kodaira, Tokyo 187-8502, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Kato
authors.affiliation: Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry4-1-1 Ogawa-Higashi, KodairaTokyo187-8502, Japan.
authors.forename: Chisato
authors.initials: C
authors.lastname: Wakabayashi
authors.affiliation: Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry4-1-1 Ogawa-Higashi, KodairaTokyo187-8502, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kunugi
mesh_terms: D000818:Animals; D001549:Benzamides; D015415:Biomarkers / Q000378:metabolism; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D006801:Humans; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D008774:Methylphenidate / Q000494:pharmacology*; D049268:Positron-Emission Tomography / Q000379:methods; D051381:Rats; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D012559:Schizophrenia / Q000175:diagnosis / Q000378:metabolism*
chemical_list: D001549:Benzamides; D015415:Biomarkers; D000697:Central Nervous System Stimulants; D017448:Receptors, Dopamine D2; D008774:Methylphenidate; D008694:Methamphetamine; C574003:fallypride; D004298:Dopamine
keywords: Positron emission tomography; Psychostimulant; Schizophrenia; Sensitization; [(18)F]fallypride