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Targeting Neuroplasticity in Substance Use Disorders: Implications for Therapeutics
1Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, Oregon, USA;
Annual Review of Pharmacology and Toxicology
|October 7, 2024
Summary
Researchers explored synaptic plasticity in cocaine addiction, finding that calcium-permeable AMPA receptors (CP-AMPARs) in the nucleus accumbens drive persistent cocaine seeking, offering potential therapeutic targets for relapse prevention.
Area of Science:
- Neuroscience
- Addiction Research
- Molecular Psychiatry
Background:
- Substance use disorder (SUD) is linked to behavioral changes driven by synaptic plasticity.
- The nucleus accumbens is a key brain region implicated in cocaine seeking.
Purpose of the Study:
- To review advances in identifying synaptic plasticity related to cocaine use disorder.
- To focus on cocaine-induced plasticity in the nucleus accumbens and its role in cocaine seeking.
Main Methods:
- Review of drug self-administration models (extinction-reinstatement and abstinence).
- Analysis of synaptic plasticity mechanisms, particularly AMPA receptor transmission.
Main Results:
- Both models indicate a link between cocaine seeking and potentiated AMPA receptor (AMPAR) transmission in the nucleus accumbens.
- Atypical calcium-permeable AMPA receptors (CP-AMPARs) mediate cue-induced seeking, persisting after abstinence.
Conclusions:
- CP-AMPARs in the nucleus accumbens are crucial for persistent cocaine seeking, modeling relapse vulnerability in SUD.
- Strategies to reverse CP-AMPAR plasticity and target excitatory synapse components show therapeutic potential for SUD treatment.
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