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Plos One : Chronic Ketamine Administration Modulates Midbrain Dopamine System in Mice, Volume 7

By Manzoni, Olivier, Jacques

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Book Id: WPLBN0003935072
Format Type: PDF eBook :
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Reproduction Date: 2015

Title: Plos One : Chronic Ketamine Administration Modulates Midbrain Dopamine System in Mice, Volume 7  
Author: Manzoni, Olivier, Jacques
Volume: Volume 7
Language: English
Subject: Journals, Science, Medical Science
Collections: Periodicals: Journal and Magazine Collection
Publication Date:
Publisher: Plos


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Manzoni, O. J. (n.d.). Plos One : Chronic Ketamine Administration Modulates Midbrain Dopamine System in Mice, Volume 7. Retrieved from

Description : Ketamine is an anesthetic and a popular abusive drug. As an anesthetic, effects of ketamine on glutamate and GABA transmission have been well documented but little is known about its long-term effects on the dopamine system. In the present study, the effects of ketamine on dopamine were studied in vitro and in vivo. In pheochromocytoma (PC 12) cells and NGF differentiated-PC 12 cells, ketamine decreased the cell viability while increasing dopamine (DA) concentrations in a dose-related manner. However, ketamine did not affect the expression of genes involved in DA synthesis. In the long-term (3 months) ketamine treated mice, significant increases of DA contents were found in the midbrain. Increased DA concentrations were further supported by up-regulation of tyrosine hydroxylase (TH), the rate limiting enzyme in catecholamine synthesis. Activation of midbrain dopaminergic neurons could be related to ketamine modulated corticalsubcortical glutamate connections. Using western blotting, significant increases in BDNF protein levels were found in the midbrain, suggesting that perhaps BDNF pathways in the cortical-subcortical connections might contribute to the longterm ketamine induced TH upregulation. These data suggest that long-term ketamine abuse caused a delayed and persistent upregulation of subcortical DA systems, which may contribute to the altered mental status in ketamine abusers.


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