Downregulation in the human and mice cerebella after ketamine versus ketamine plus ethanol treatment

• Published in: Microscopy research and technique 2012-03, Vol.75 (3), p.258-264
• Main Authors: Chan, W.M., Xu, Jie, Fan, Ming, Jiang, Yanling, Tsui, Therese Y.M., Wai, Maria S.M., Lam, W.P., Yew, D.T.
• Format: Article
• Language: English
• Subjects: Analgesics - administration & dosage; Analgesics - adverse effects; Animals; apoptosis; Apoptosis - drug effects; Central Nervous System Depressants - administration & dosage; Central Nervous System Depressants - adverse effects; cerebellum; Cerebellum - drug effects; Cerebellum - metabolism; Drug Interactions; ethanol; Ethanol - administration & dosage; Ethanol - adverse effects; fMRI; Humans; Image Interpretation, Computer-Assisted; In Situ Nick-End Labeling; ketamine; Ketamine - administration & dosage; Ketamine - adverse effects; Magnetic Resonance Imaging; Male; Mice; Mice, Inbred ICR; Motor Activity - drug effects; Substance-Related Disorders - physiopathology
• ISSN: 1059-910X; 1097-0029
• DOI: 10.1002/jemt.21052

To study the deleterious effects of ketamine and the potential interaction effects between ethanol and ketamine on the cerebellum, functional magnetic resonance imaging (fMRI) tests were performed on the habitual ketamine users (n = 3) when they flexed and extended their upper limbs. Another fMRI test was performed on the same participants in which they consumed alcohol (12%, 200 mL) 1 h before the test. Downregulation on the activity of cerebellum was observed and the level of activation in the cerebellum decreased dramatically in habitual ketamine users with alcohol consumption before the test. Further studies were performed by using male ICR mice receiving treatment of ketamine only [30 mg kg−1 intraperitoneally (i.p.)] or ethanol only everyday (0.5 mL 12% orally) and those with coadministration of the above dosages of ketamine and ethanol for 3 months. Fewer Purkinje cells were observed in the cerebellar sections of ketamine treated mice under silver staining. For TUNEL test, a significant increase in the apoptotic cells were observed in the cerebella of the ketamine treated mice (P = 0.016) and of those with co‐administration of ketamine and ethanol (P < 0.001), when compared with the control. A statistical significance (P < 0.001) in two‐way ANOVA test indicated that there might be an interactive mechanism between ethanol and ketamine acting on the cerebellum. Microsc. Res. Tech. 2011. © 2011 Wiley Periodicals, Inc.