Journal
NEUROSCIENCE LETTERS
Volume 440, Issue 3, Pages 319-322Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.neulet.2008.05.106
Keywords
schizophrenia; nicotine; ketamine; dopamine; glutamate; NMDA
Categories
Ask authors/readers for more resources
Nicotine evokes dopamine release through activation of nicotinic acetylcholine receptors, and tobacco cigarette smoking is more prevalent among individuals diagnosed with schizophrenia. Blockade of ionotropic glutamate (NMDA) receptors can induce changes in central dopamine and glutamate circuits, which models the symptoms of schizophrenia. The effect of the NMDA receptor antagonist, ketamine, on the effect of nicotine in rat prefrontal cortex was examined using a slice superfusion assay in which cortical slices were preloaded with [H-3] dopamine. A wide range of ketamine concentrations (0.1-300 mu M) did not evoke [H-3] overflow from slices, indicating that NMDA receptor blockade did not induce dopamine release. Ketamine, at concentrations that model the symptoms of schizophrenia (1-10 mu M), augmented the effect of nicotine (1-100 mu M) to evoke [H-3] overflow from slices and decreased the threshold nicotine concentration to evoke [3 HI overflow. This indicates that NMDA receptor blockade increased the potency and efficacy of nicotine to evoke dopamine release from prefrontal cortex slices, suggesting that ketamine induced hypersensitivity to nicotine. The present results support a role for nicotinic acetylcholine receptors in the pathophysiology and treatment of schizophrenia. (C) 2008 Elsevier Ireland Ltd. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available