HDAC Inhibitor Infusion and Behavioral Testing
Objective: To assess antidepressant-like effects of HDAC inhibitor MS-275 infusion into the nucleus accumbens using behavioral assays
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Protocol Steps
Chronic social defeat stress exposure
Subjects exposed to chronic social defeat stress paradigm prior to HDAC inhibitor infusion
Note: This stress paradigm produces persistent increase in H3 acetylation in nucleus accumbens
View evidence from paper
“chronic social defeat stress in mice causes a transient decrease, followed by a persistent increase, in levels of acetylated histone H3 in the nucleus accumbens”
HDAC inhibitor infusion into nucleus accumbens
Infusion of MS-275 HDAC inhibitor directly into the nucleus accumbens to increase histone acetylation
Note: Infusion increases histone acetylation and produces antidepressant-like effects
View evidence from paper
“infusion of HDAC inhibitors into the nucleus accumbens, which increases histone acetylation, exerts robust antidepressant-like effects in the social defeat paradigm and other behavioral assays”
Behavioral assays
Conduct behavioral testing to assess antidepressant-like effects following HDAC inhibitor infusion
Note: Multiple behavioral assays used to measure antidepressant-like effects
View evidence from paper
“exerts robust antidepressant-like effects in the social defeat paradigm and other behavioral assays”
Gene expression analysis
Collect nucleus accumbens tissue and perform microarray analysis to determine global patterns of gene expression
Note: Results compared to effects of fluoxetine treatment
View evidence from paper
“HDAC inhibitor infusion also reverses the effects of chronic defeat stress on global patterns of gene expression in the nucleus accumbens, as determined by microarray analysis”