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Chronic Nicotine Exposure Alters Metabotropic Glutamate Receptor 5: Longitudinal PET Study and Behavioural Assessment in Rats.
Müller Herde, Adrienne; Mihov, Yoan; Krämer, Stefanie D; Mu, Linjing; Adamantidis, Antoine; Ametamey, Simon M; Hasler, Gregor.
Afiliação
  • Müller Herde A; Center for Radiopharmaceutical Sciences of ETH, PSI, and USZ, Department of Chemistry and Applied Biosciences of ETH, 8093, Zurich, Switzerland.
  • Mihov Y; Translational Research Center, University Hospital of Psychiatry, University of Bern, 3000, Bern 60, Switzerland.
  • Krämer SD; Center for Radiopharmaceutical Sciences of ETH, PSI, and USZ, Department of Chemistry and Applied Biosciences of ETH, 8093, Zurich, Switzerland.
  • Mu L; Department of Nuclear Medicine, University Hospital Zurich, Center for Radiopharmaceutical Sciences of ETH, PSI, and USZ, 8091, Zurich, Switzerland.
  • Adamantidis A; Department of Biomedical Research, Inselspital University Hospital, University of Bern, 3000, Bern, Switzerland.
  • Ametamey SM; Centre for Experimental Neurology, Department of Neurology, Inselspital University Hospital, University of Bern, Bern, Switzerland.
  • Hasler G; Center for Radiopharmaceutical Sciences of ETH, PSI, and USZ, Department of Chemistry and Applied Biosciences of ETH, 8093, Zurich, Switzerland.
Neurotox Res ; 36(4): 806-816, 2019 Nov.
Article em En | MEDLINE | ID: mdl-31119680
ABSTRACT
Using positron emission tomography (PET), a profound alteration of the metabotropic glutamate receptor 5 (mGluR5) was found in human smoking addiction and abstinence. As human PET data either reflect the impact of chronic nicotine exposure or a pre-existing vulnerability to nicotine addiction, we designed a preclinical, longitudinal study to investigate the effect of chronic nicotine exposure on mGluR5 with the novel radiotracer [18F]PSS232 using PET. Twelve male dark Agouti rats at the age of 6 weeks were assigned randomly to three groups. From day 0 to day 250 the groups received 0 mg/L, 4 mg/L, or 8 mg/L nicotine solution in the drinking water. From day 250 to 320 all groups received nicotine-free drinking water. PET scans with [18F]PSS232 were performed in all animals on days 0, 250, and 320. To assess locomotion, seven tests in square open field arenas were carried out 72 days after the last PET scan. During the first four tests, rats received 0 mg/L nicotine and for the last three tests 4 mg/L nicotine in the drinking water. After 250 days of nicotine consumption [18F]PSS232 binding was reduced in the striatum, hippocampus, thalamus, and midbrain. At day 320, after nicotine withdrawal, [18F]PSS232 binding increased. These effects were more pronounced in the 4 mg/L nicotine group. Chronic administration of nicotine through the drinking water reduced exploratory behaviour. This preliminary longitudinal PET study demonstrates that chronic nicotine administration alters behaviour and mGluR5 availability. Chronic nicotine administration leads to decreased [18F]PSS232 binding which normalizes after prolonged nicotine withdrawal.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Encéfalo / Receptor de Glutamato Metabotrópico 5 / Atividade Motora / Nicotina Idioma: En Ano de publicação: 2019 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Encéfalo / Receptor de Glutamato Metabotrópico 5 / Atividade Motora / Nicotina Idioma: En Ano de publicação: 2019 Tipo de documento: Article