ArticleProceedings of the National Academy of Sciences of the United States of America2020
Neuroadaptations in the dorsal hippocampus underlie cocaine seeking during prolonged abstinence.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 43 citations in OpenAlex.
- Large-scale reorganization of DNA methylation and upregulation of extracellular matrix genes in the dorsal dentate gyrus following cocaine taking.bioRxiv : the preprint server for biology · 2026Article
- GABAFrontiers in pharmacology · 2026Review
- The ventral hippocampus and nucleus accumbens as neural substrates for cocaine contextual memory reconsolidation.Translational psychiatry · 2025Article
- The Top-Down of Prefrontal Cortex to the Hippocampus Glutamatergic Pathway Regulates Reward Memory of Methamphetamine.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Sex-specific dysregulation of the CXProgress in neuro-psychopharmacology & biological psychiatry · 2025Article
- Multi-omics Analysis Reveals miR-7220-5p Alleviates NThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Article
- Spatiotemporal terahertz modulation enhances NMDAR-mediated miniature EPSCs.Scientific reports · 2025Article
- A Novel Role for the Histone Demethylase JMJD3 in Mediating Heroin-Induced Relapse-Like Behaviors.Biological psychiatry · 2025Article
- Neurobiology of the incubation of drug craving: An update.Pharmacological reviews · 2025Review
- Sex-specific effects of chronic stress prior to cocaine exposure on cue- vs drug-induced relapse after prolonged abstinence.Behavioural brain research · 2024Article
- Intrinsic Functional Connectivity between the Anterior Insular and Retrosplenial Cortex as a Moderator and Consequence of Cocaine Self-Administration in Rats.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Factors Associated with Relapses in Alcohol and Substance Use Disorder.The Eurasian journal of medicine · 2023Article
- Single-nucleus genomics in outbred rats with divergent cocaine addiction-like behaviors reveals changes in amygdala GABAergic inhibition.Nature neuroscience · 2023Article
- Impaired synaptic transmission in dorsal dentate gyrus increases impulsive alcohol seeking.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023Article
- Role of Microglia in Psychostimulant Addiction.Current neuropharmacology · 2023Review
- Overnight Abstinence Is Associated With Smaller Secondary Somatosensory Cortical Volumes and Higher Somatosensory-Motor Cortical Functional Connectivity in Cigarette Smokers.Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2022Article
- Metabolites of Cannabis Induce Cardiac Toxicity and Morphological Alterations in Cardiac Myocytes.International journal of molecular sciences · 2022Article
- Neuroadaptations and TGF-β signaling: emerging role in models of neuropsychiatric disorders.Molecular psychiatry · 2022Review
- Activin A Reduces GIRK Current to Excite Dentate Gyrus Granule Cells.Frontiers in cellular neuroscience · 2022Article
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15 authors at 4 institutions in 2 countries.
Funding
Abstract
Relapse vulnerability in substance use disorder is attributed to persistent cue-induced drug seeking that intensifies (or "incubates") during drug abstinence. Incubated cocaine seeking has been observed in both humans with cocaine use disorder and in preclinical relapse models. This persistent relapse vulnerability is mediated by neuroadaptations in brain regions involved in reward and motivation. The dorsal hippocampus (DH) is involved in context-induced reinstatement of cocaine seeking but the role of the DH in cocaine seeking during prolonged abstinence has not been investigated. Here we found that transforming growth factor-β (TGF-β) superfamily member activin A is increased in the DH on abstinence day (AD) 30 but not AD1 following extended-access cocaine self-administration compared to saline controls. Moreover, activin A does not affect cocaine seeking on AD1 but regulates cocaine seeking on AD30 in a bidirectional manner. Next, we found that activin A regulates phosphorylation of NMDA receptor (NMDAR) subunit GluN2B and that GluN2B-containing NMDARs also regulate expression of cocaine seeking on AD30. Activin A and GluN2B-containing NMDARs have both previously been implicated in hippocampal synaptic plasticity. Therefore, we examined synaptic strength in the DH during prolonged abstinence and observed an increase in moderate long-term potentiation (LTP) in cocaine-treated rats compared to saline controls. Lastly, we examined the role of DH projections to the lateral septum (LS), a brain region implicated in cocaine seeking and found that DH projections to the LS govern cocaine seeking on AD30. Taken together, this study demonstrates a role for the DH in relapse behavior following prolonged abstinence from cocaine self-administration.
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