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Spectral Confocal Imaging of Fluorescently tagged Nicotinic Receptors in Knock-in Mice with Chronic Nicotine Administration
Published on: February 10, 2012
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Impact of Serine Racemase Deletion on Nicotine Discrimination
Isabel L Yu1,2, Joseph T Coyle1,3, Rajeev I Desai1,2
1Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
Summary
Mice with schizophrenia-related gene mutations showed reduced sensitivity to nicotine's effects, suggesting a potential reason for increased smoking in schizophrenia patients. This highlights the role of N-methyl-d-aspartate receptors in nicotine addiction.
Area of Science:
- Neuroscience
- Psychiatry
- Genetics
Background:
- Schizophrenia and smoking often co-occur, suggesting shared genetic influences.
- The N-methyl-d-aspartate (NMDA) receptor is implicated in both schizophrenia and nicotine addiction.
Purpose of the Study:
- To investigate the role of NMDA receptor hypofunction in nicotine sensitivity using a mouse model of schizophrenia.
- To determine if serine racemase gene (srr) knockout affects nicotine discrimination.
Main Methods:
- Utilized serine racemase knockout (srr-/-) mice, a model for schizophrenia with NMDA receptor hypofunction.
- Employed established nicotine discrimination procedures with wild-type (WT) and srr-/- mice.
Main Results:
- WT mice successfully acquired nicotine discrimination, while srr-/- mice failed even with extended training.
- NMDA receptor hypofunction in srr-/- mice significantly reduced their sensitivity to nicotine's interoceptive effects.
Conclusions:
- NMDA receptor hypofunction, potentially due to serine racemase gene mutations in schizophrenia, may decrease nicotine sensitivity.
- This reduced sensitivity could drive increased nicotine consumption in individuals with schizophrenia to achieve desired effects.
