Department of Biomedical Imaging and Radiological Science, China Medical University, 91 Hsueh-Shih Road, Taichung, 40402, Taiwan.
Center for Advanced Molecular Imaging and Translation, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
Psychopharmacology (Berl). 2019 Jun;236(6):1749-1757. doi: 10.1007/s00213-018-5157-4. Epub 2019 Jan 2.
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.
咖啡因是一种广泛研究的精神兴奋剂，尽管其对大脑活动的确切影响仍有待阐明。正电子发射断层扫描（PET）允许研究咖啡因对未接受咖啡因的大鼠大脑代谢反应的机制。啮齿动物研究通常在麻醉下进行。然而，麻醉可能会影响测试药物靶向的神经递质系统。
本研究旨在探讨两种常见麻醉剂α-氯醛和异氟醚对咖啡因动力学的影响是抑制还是增强。
第一组大鼠（n=15）在 1.5%异氟醚麻醉下麻醉。第二组大鼠（n=15）在α-氯醛（80mg/kg）麻醉下麻醉。这两组大鼠分别静脉注射生理盐水（n=5）或 2.5mg/kg（n=5）或 40mg/kg（n=5）咖啡因。
在α-氯醛麻醉下，2.5mg/kg 或 40mg/kg 咖啡因分别使全脑脑代谢降低 17.2%和 17%（均 P<0.01）。然而，较低剂量的咖啡因（2.5mg/kg）对脑代谢的影响有限，而较高剂量的咖啡因（40mg/kg）在异氟醚麻醉下使纹状体、海马和丘脑的脑代谢增强（均 P<0.05）。
这些发现表明，基于使用的麻醉方案，大脑对咖啡因的反应存在显著差异，这强调了在解释动物药理学研究结果时注意麻醉剂的重要性，因为麻醉剂和研究药物之间可能存在相互作用。
