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Environmental Modulations of the Number of Midbrain Dopamine Neurons in Adult Mice
Published on: January 20, 2015
Chronic ketamine administration modulates midbrain dopamine system in mice.
Sijie Tan1, Wai Ping Lam, Maria S M Wai
1Brain Research Center, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, PR China.
Plos One
|September 1, 2012
Summary
Long-term ketamine abuse increases dopamine levels in the brain, particularly in the midbrain. This persistent change in the dopamine system may be linked to altered mental states observed in ketamine users.
Area of Science:
- Neuroscience
- Pharmacology
Background:
- Ketamine is an anesthetic with known effects on glutamate and GABA.
- Limited understanding exists regarding ketamine's long-term impact on the dopamine system.
Purpose of the Study:
- To investigate the in vitro and in vivo effects of ketamine on the dopamine system.
- To explore the molecular mechanisms underlying ketamine's long-term dopaminergic effects.
Main Methods:
- In vitro studies using PC 12 cells.
- In vivo studies involving long-term ketamine administration in mice.
- Gene expression analysis and Western blotting to assess dopamine synthesis and BDNF levels.
Main Results:
- Ketamine decreased cell viability but increased dopamine concentrations in PC 12 cells.
- Long-term ketamine treatment in mice led to increased midbrain dopamine levels and tyrosine hydroxylase (TH) expression.
- Elevated BDNF protein levels were observed in the midbrain of treated mice.
Conclusions:
- Long-term ketamine abuse induces a delayed and persistent upregulation of subcortical dopamine systems.
- Ketamine-induced changes in tyrosine hydroxylase may involve BDNF pathways and altered cortical-subcortical glutamate connections.
- These neurochemical alterations may contribute to the altered mental status associated with ketamine abuse.
