The effect of caffeine on cerebral metabolism during alpha-chloralose anesthesia differs from isoflurane anesthesia in the rat brain

  • Shin-Lei PengEmail author
  • Han Chiu
  • Chun-Yi Wu
  • Chiun-Wei Huang
  • Yi-Hsiu Chung
  • Cheng-Ting Shih
  • Wu-Chung Shen
Original Investigation



Caffeine is a widely studied psychostimulant, even though its exact effect on brain activity remains to be elucidated. Positron emission tomography (PET) allows studying mechanisms underlying cerebral metabolic responses to caffeine in caffeine-naïve rats. Rodent studies are typically performed under anesthesia. However, the anesthesia may affect neurotransmitter systems targeted by tested drugs.


The scope of the present study was to address the impairing or enhancing effect of two common anesthetics, alpha-chloralose and isoflurane, on the kinetics of caffeine.


The first group of rats (n = 15) were anesthetized under 1.5% isoflurane anesthesia. The second group of rats (n = 15) were anesthetized under alpha-chloralose (80 mg/kg). These rats received an intravenous injection of saline (n = 5) or of 2.5 mg/kg (n = 5) or 40 mg/kg (n = 5) caffeine for both groups.


With 2.5 mg/kg or 40 mg/kg caffeine, whole-brain cerebral metabolism was significantly reduced by 17.2% and 17% (both P < 0.01), respectively, under alpha-chloralose anesthesia. However, the lower dose of caffeine (2.5 mg/kg) had a limited effect on brain metabolism, whereas its higher dose (40 mg/kg) produced enhancements in brain metabolism in the striatum, hippocampus, and thalamus (all P < 0.05) under isoflurane anesthesia.


These findings demonstrate significant differences in brain responses to caffeine on the basic of the anesthesia regimen used, which highlights the importance of attention to the anesthetic used when interpreting findings from animal pharmacological studies because of possible interactions between the anesthetic and the drug under study.


PET Cerebral metabolism Caffeine Anesthesia Concentration 18F-FDG 


Funding information

This work was funded by Ministry of Science Technology (MOST 105-2314-B-039-044-MY2).

Compliance with ethical standards

All animal experiments were approved by China Medical University Institutional Animal Care and Use Committee and were carried out in accordance with the approved guidelines.

Conflict of interest

The authors declare that there are no competing interests.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Biomedical Imaging and Radiological ScienceChina Medical UniversityTaichungTaiwan
  2. 2.Center for Advanced Molecular Imaging and TranslationChang Gung Memorial HospitalTaoyuanTaiwan
  3. 3.Department of Medical Imaging and Radiological SciencesChung Shan Medical UniversityTaichungTaiwan
  4. 4.Department of RadiologyChina Medical University HospitalTaichungTaiwan

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