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Using Optogenetics to Reverse Neuroplasticity and Inhibit Cocaine Seeking in Rats
Published on: October 5, 2021
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ADAR2-dependent GluA2 editing regulates cocaine seeking
H D Schmidt1, K N McFarland2, S B Darnell3
1Center for Neurobiology and Behavior, Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Molecular Psychiatry
|October 29, 2014
Summary
Reduced editing of GluA2 subunits in the nucleus accumbens shell impairs cocaine seeking. Overexpressing ADAR2b in this region promotes editing and reduces relapse behaviors, suggesting a new therapeutic target for cocaine addiction.
Area of Science:
- Neuroscience
- Molecular Biology
- Pharmacology
Background:
- Activation of AMPA receptors (AMPARs) in the nucleus accumbens is crucial for cocaine-seeking behavior.
- Calcium-permeable AMPARs (CP-AMPARs), formed by unedited GluA2(Q) subunits, are implicated in cocaine relapse.
- The role of GluA2 Q/R site editing and ADAR2 in cocaine seeking remains unclear.
Purpose of the Study:
- To investigate the impact of cocaine abstinence on GluA2 Q/R site editing and ADAR2 expression in the rat nucleus accumbens.
- To determine the functional significance of ADAR2 and GluA2 Q/R site editing in cocaine seeking.
Main Methods:
- Assessed GluA2 Q/R site editing and ADAR2 expression in cocaine-experienced rats after forced abstinence.
- Utilized viral-mediated gene delivery to overexpress ADAR2b in the nucleus accumbens shell.
- Measured cocaine priming-induced reinstatement of drug seeking.
Main Results:
- Cocaine abstinence decreased GluA2 Q/R site editing and ADAR2 expression in the accumbens shell.
- Overexpression of ADAR2b in the accumbens shell attenuated cocaine-seeking behavior.
- Increased ADAR2b expression led to enhanced GluA2 Q/R site editing and surface expression of GluA2-containing AMPARs.
Conclusions:
- Reduced GluA2 Q/R site editing and ADAR2 expression in the accumbens shell are associated with cocaine seeking.
- CP-AMPARs containing unedited GluA2(Q) subunits in the accumbens shell promote cocaine seeking.
- Targeting CP-AMPARs represents a novel therapeutic strategy for cocaine addiction.
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