Learned Helplessness Paradigm
Objective: To assess antidepressant-like effects in transgenic and viral-mediated gene transfer mice using the learned helplessness paradigm, a behavioral model of depression
This is a Learned Helplessness Paradigm protocol using mouse as the model organism. The procedure involves 6 procedural steps, 1 equipment items. Extracted from a 2002 paper published in Journal of Neuroscience.
Model and subjects
mouse • transgenic lines expressing CREB or dominant-negative mutant of CREB (mCREB) in forebrain regions • unknown • not specified • not specified
Study window
Estimated timing pending
Core workflow
Generate transgenic mouse lines • Perform viral-mediated gene transfer • Conduct learned helplessness testing
Primary readouts
- Antidepressant-like effects in learned helplessness paradigm
- CREB expression levels
- mCREB expression levels
- Prodynorphin expression in nucleus accumbens medium spiny neurons
Key equipment and reagents
Verified items
0
Direct vendor links
0
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Protocol Steps
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Generate transgenic mouse lines
Develop inducible transgenic lines of mice that express either CREB or a dominant-negative mutant of CREB (mCREB) in forebrain regions
Note: Two transgenic conditions: CREB overexpression and mCREB (dominant-negative) expression
View evidence from paper
“We developed inducible transgenic lines of mice that express either CREB or a dominant-negative mutant of CREB (mCREB) in forebrain regions”
Perform viral-mediated gene transfer
Use complementary viral-mediated gene transfer approach to directly test the effect of mCREB in the nucleus accumbens
Note: Nucleus accumbens is a brain region important for motivation and reward
View evidence from paper
“We also use a complementary viral-mediated gene transfer approach to directly test the effect of mCREB in the nucleus accumbens, a brain region important for motivation and reward”
Conduct learned helplessness testing
Test transgenic mice and viral-mediated gene transfer mice in the learned helplessness paradigm to assess antidepressant-like effects
Note: Behavioral model of depression used to measure antidepressant-like effects
View evidence from paper
“used these mice to determine the functional significance of this transcription factor in the learned helplessness paradigm, a behavioral model of depression”
Assess CREB blockade effects
Evaluate antidepressant-like effects produced by blockade of CREB through overexpression of mCREB in transgenic mice or viral expression of mCREB in nucleus accumbens
Note: Compare with CREB overexpression which produces opposite phenotype
View evidence from paper
“blockade of CREB by overexpression of mCREB in transgenic mice or by viral expression of mCREB in the nucleus accumbens produces an antidepressant-like effect, whereas overexpression of CREB in transgenic mice results in the opposite phenotype”
Analyze prodynorphin expression
Examine colocalization of mCREB with prodynorphin and measure decreased expression of prodynorphin in nucleus accumbens medium spiny neurons
Note: mCREB expression was colocalized with and decreased prodynorphin expression
View evidence from paper
“mCREB expression was colocalized with and decreased the expression of prodynorphin in nucleus accumbens medium spiny neurons”
Test dynorphin antagonism
Administer dynorphin antagonism in the nucleus accumbens to assess antidepressant-like effects
Note: Antagonism of dynorphin produces antidepressant-like effect similar to CREB blockade
View evidence from paper
“antagonism of dynorphin in the nucleus accumbens was sufficient to produce an antidepressant-like effect similar to that observed after blockade of CREB”