ArticleProceedings of the National Academy of Sciences of the United States of America2016
Re-silencing of silent synapses unmasks anti-relapse effects of environmental enrichment.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 53 citations in OpenAlex.
- Incubation of oxycodone craving is associated with CP-AMPAR upregulation in D1 and A2a receptor-expressing medium spiny neurons in nucleus accumbens core and shell.Neuropharmacology · 2026Article
- Activation of silent synapses driven by emerging technologies: mechanisms, disease associations, and prospects for clinical translation.Frontiers in synaptic neuroscience · 2026Review
- A coordinated and enhanced brain network supports the persistence of long-term cocaine memory.Translational psychiatry · 2025Article
- Neurobiology of the incubation of drug craving: An update.Pharmacological reviews · 2025Review
- Targeting Neuroplasticity in Substance Use Disorders: Implications for Therapeutics.Annual review of pharmacology and toxicology · 2025Review
- Dietary regulation of silent synapses in the dorsolateral striatum.Neuroscience · 2024Article
- DIETARY REGULATION OF SILENT SYNAPSES IN THE DORSOLATERAL STRIATUM.bioRxiv : the preprint server for biology · 2024Article
- An EEG Signature of MCH Neuron Activities Predicts Cocaine Seeking.bioRxiv : the preprint server for biology · 2024Article
- Increased Excitability of Layer 2 Cortical Pyramidal Neurons in the Supplementary Motor Cortex Underlies High Cocaine-Seeking Behaviors.Biological psychiatry · 2023Article
- mGlu5 inhibition in the basolateral amygdala prevents estrous cycle-dependent changes in cue-induced cocaine seeking.Addiction neuroscience · 2023Article
- Impaired synaptic transmission in dorsal dentate gyrus increases impulsive alcohol seeking.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023Article
- Effects of prenatal opioid exposure on synaptic adaptations and behaviors across development.Neuropharmacology · 2023Review
- Rapid Eye Movement Sleep Engages Melanin-Concentrating Hormone Neurons to Reduce Cocaine Seeking.Biological psychiatry · 2022Article
- Amyloid-β oligomers in the nucleus accumbens decrease motivation via insertion of calcium-permeable AMPA receptors.Molecular psychiatry · 2022Article
- Use of prepubertal environment enrichment to prevent dopamine dysregulation in a neurodevelopmental rat model of schizophrenia risk.STAR protocols · 2022Article
- Cocaine-induced projection-specific and cell type-specific adaptations in the nucleus accumbens.Molecular psychiatry · 2022Review
- Factors modulating the incubation of drug and non-drug craving and their clinical implications.Neuroscience and biobehavioral reviews · 2021Review
- Isolation housing elevates amphetamine seeking independent of nucleus accumbens glutamate receptor adaptations.The European journal of neuroscience · 2021Article
- microRNA regulation related to the protective effects of environmental enrichment against cocaine-seeking behavior.Drug and alcohol dependence · 2021Article
- AMPA and NMDA Receptor Trafficking at Cocaine-Generated Synapses.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Environmental enrichment (EE) has long been postulated as a behavioral treatment for drug addiction based on its preventive effects in animal models: rodents experiencing prior EE exhibit increased resistance to establishing drug taking and seeking. However, the therapeutic effects of EE, namely, the effects of EE when applied after drug exposure, are often marginal and transient. Using incubation of cue-induced cocaine craving, a rat relapse model depicting progressive intensification of cocaine seeking after withdrawal from cocaine self-administration, our present study reveals that after cocaine withdrawal, in vivo circuit-specific long-term depression (LTD) unmasks the therapeutic power of EE to achieve long-lasting anti-relapse effects. Specifically, our previous results show that cocaine self-administration generates AMPA receptor (AMPAR)-silent excitatory synapses within the basolateral amygdala (BLA) to nucleus accumbens (NAc) projection, and maturation of these silent synapses via recruiting calcium-permeable (CP) AMPARs contributes to incubation of cocaine craving. Here, we show that after cocaine withdrawal and maturation of silent synapses, the BLA-to-NAc projection became highly resistant to EE. However, optogenetic LTD applied to this projection in vivo transiently re-silenced these silent synapses by removing CP-AMPARs. During this transient window, application of EE resulted in the insertion of nonCP-AMPARs, thereby remodeling the "incubated" BLA-to-NAc projection. Consequently, incubation of cocaine craving was decreased persistently. These results reveal a mechanistic basis through which the persistent anti-relapse effects of EE can be unleashed after drug withdrawal.
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