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Inducible and brain region-specific CREB transgenic mice
Norio Sakai1, Johannes Thome, Samuel S Newton
1Division of Molecular Psychiatry, Department of Psychiatry, Yale University School of Medicine and Connecticut Mental Health Center, New Haven, Connecticut 06508, USA.
Molecular Pharmacology
|May 22, 2002
Summary
This study developed CREB transgenic mice to explore drug responses. CREB overexpression altered gene expression and reduced cocaine-induced activity, suggesting CREB
Area of Science:
- Neuroscience
- Molecular Biology
- Pharmacology
Background:
- The cAMP response element-binding protein (CREB) is crucial for neuronal plasticity and adaptation.
- Understanding CREB's role in psychotropic drug responses is essential for developing targeted therapies.
Purpose of the Study:
- To investigate the function of CREB in adaptive responses to psychotropic drugs.
- To create a tool for studying CREB's role in specific brain regions.
Main Methods:
- Developed inducible, brain region-specific CREB transgenic mice using the tetracycline-regulated gene expression system.
- Utilized the neuron-specific enolase (NSE) promoter to control CREB overexpression.
- Administered doxycycline to block CREB expression.
Main Results:
- Achieved varied CREB overexpression patterns in the striatum, nucleus accumbens, and cingulate cortex.
- Observed CREB overexpression influencing other CREB/ATF transcription factors.
- Found psychostimulant induction of dynorphin was upregulated in the striatum.
- Demonstrated a significant reduction in cocaine-induced locomotor activity in CREB transgenic mice.
Conclusions:
- CREB plays a significant role in mediating adaptive changes in response to psychotropic drugs.
- CREB transgenic mice provide a valuable model for studying drug addiction and neuroadaptation.