title: In vivo [¹⁸F] FDG PET imaging reveals that p-chloroamphetamine neurotoxicity is associated with long-term cortical and hippocampal hypometabolism.
abstract: OBJECTIVE
  p-Chloroamphetamine (PCA) is a neurotoxin that selectively degenerates the serotonin (5-HT) axon terminals. In order to study the brain metabolic consequences induced by serotonergic denervation, a single dose of PCA (2.5 or 10 mg/kg i.p.) was administered to male adult rats.
  
  
  METHODS
  In vivo regional brain metabolism was evaluated 3 and 21 days after PCA (2.5 or 10 mg/kg; i.p.) injection by 2-deoxy-2-[(18)F] fluoro-D-glucose ([(18)F] FDG) positron emission tomography (PET). At day 22, the following markers of neurotoxicity were determined: (a) 5-HT axon terminal lesion by 5-HT transporter (SERT) autoradiography, (b) reactive gliosis by glial fibrillary acidic protein immunohistochemistry, and (c) eventual neurodegeneration by DAPI/Fluoro-Jade C labeling.
  
  
  RESULTS
  An average of 20 % reduction of [(18)F] FDG uptake in most brain areas was observed at day 21 under 10 mg/kg PCA treatment. Instead, 2.5 mg/kg PCA only reduced metabolic activity in neocortex. Likewise, the high dose of PCA exerted a strong decrease (>30 %) in SERT density in several 5-HT innervated regions, but no effect was found in midbrain raphe nuclei, the main source of serotonergic neurons. Although PCA induced astroglial activation both in hippocampus and cortex in response to axotomy, no signs of neuronal death in these areas were detected.
  
  
  CONCLUSIONS
  Overall, [(18)F] FDG PET revealed that the reduction of the brain metabolic activity induced by PCA is related to 5-HT axon terminal lesion, with no apparent affectation of neuronal viability.
authors.affiliation: Departamento de Farmacología, Facultad de Farmacia, Universidad Complutense de Madrid, Plaza Ramón y Cajal s/n, 28040, Madrid, Spain, lgarciag@ucm.es.
authors.forename: Luis
authors.initials: L
authors.lastname: García-García
authors.forename: Mercedes
authors.initials: M
authors.lastname: Delgado
authors.forename: Ahmed Anis
authors.initials: AA
authors.lastname: Al-Sayed
authors.forename: Pablo
authors.initials: P
authors.lastname: Bascuñana
authors.forename: Rubén
authors.initials: R
authors.lastname: Fernández de la Rosa
authors.forename: Paloma
authors.initials: P
authors.lastname: Bermejo-Bescós
authors.forename: Sagrario
authors.initials: S
authors.lastname: Martín-Aragón
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Pozo
mesh_terms: D000818:Animals; D001345:Autoradiography; D005452:Fluoresceins / Q000378:metabolism; D019788:Fluorodeoxyglucose F18; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006624:Hippocampus / Q000000981:diagnostic imaging* / Q000187:drug effects / Q000378:metabolism*; D007150:Immunohistochemistry; D007211:Indoles / Q000378:metabolism; D008297:Male; D009410:Nerve Degeneration / Q000000981:diagnostic imaging / Q000473:pathology; D009498:Neurotoxins / Q000633:toxicity*; D049268:Positron-Emission Tomography; D017207:Rats, Sprague-Dawley; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism; D010133:p-Chloroamphetamine / Q000633:toxicity*
chemical_list: D005452:Fluoresceins; D005904:Glial Fibrillary Acidic Protein; D007211:Indoles; D009498:Neurotoxins; D050486:Serotonin Plasma Membrane Transport Proteins; C534582:fluoro-jade C; D019788:Fluorodeoxyglucose F18; C007293:DAPI; D010133:p-Chloroamphetamine; D005947:Glucose