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.
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-[18F] fluoro-d-glucose ([18F] 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.
An average of 20 % reduction of [18F] 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.
Overall, [18F] 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.
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We thank Dr. José Luis López-Lacomba, director of the Instituto de Estudios Biofuncionales UCM, and Dr. Enrique Martínez-Campos for their assistance in the use of the fluorescence microscope.
This work was financially supported by grants from the Spanish Ministerio de Ciencia e Innovación (SAF2009-09020) and Comunidad de Madrid (I2M2, S2010/BMD-2349).
Conflict of Interest
The authors declare that they have no conflict of interest.
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García-García, L., Delgado, M., Al-Sayed, A.A. et al. In Vivo [18F] FDG PET Imaging Reveals that p-Chloroamphetamine Neurotoxicity is Associated with Long-Term Cortical and Hippocampal Hypometabolism. Mol Imaging Biol 17, 239–247 (2015). https://doi.org/10.1007/s11307-014-0794-4
- [18F] FDG PET
- Fluoro-Jade C