| http://purl.uniprot.org/citations/36056105 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/36056105 | http://www.w3.org/2000/01/rdf-schema#comment | "Cocaine self-administration can disrupt the capacity of humans and rodents to flexibly modify familiar behavioral routines, even when they become maladaptive or unbeneficial. However, mechanistic factors, particularly those driving long-term behavioral changes, are still being determined. Here, we capitalized on individual differences in oral cocaine self-administration patterns in adolescent mice and revealed that the post-synaptic protein PSD-95 was reduced in the orbitofrontal cortex (OFC) of escalating, but not stable, responders, which corresponded with later deficits in flexible decision-making behavior. Meanwhile, NMDA receptor GluN2B subunit content was lower in the OFC of mice that were resilient to escalatory oral cocaine seeking. This discovery led us to next co-administer the GluN2B-selective antagonist ifenprodil with cocaine, blocking the later emergence of cocaine-induced decision-making abnormalities. GluN2B inhibition also prevented cocaine-induced dysregulation of neuronal structure and function in the OFC, preserving mature, mushroom-shaped dendritic spine densities on deep-layer pyramidal neurons, which were otherwise lower with cocaine, and safeguarding functional BLA→OFC connections necessary for action flexibility. We posit that cocaine potentiates GluN2B-dependent signaling, which triggers a series of durable adaptations that result in the dysregulation of post-synaptic neuronal structure in the OFC and disruption of BLA→OFC connections, ultimately weakening the capacity for flexible choice. And thus, inhibiting GluN2B-NMDARs promotes resilience to long-term cocaine-related sequelae."xsd:string |
| http://purl.uniprot.org/citations/36056105 | http://purl.org/dc/terms/identifier | "doi:10.1038/s41386-022-01437-8"xsd:string |
| http://purl.uniprot.org/citations/36056105 | http://purl.uniprot.org/core/author | "Pitts E.G."xsd:string |
| http://purl.uniprot.org/citations/36056105 | http://purl.uniprot.org/core/author | "Gourley S.L."xsd:string |
| http://purl.uniprot.org/citations/36056105 | http://purl.uniprot.org/core/author | "Li D.C."xsd:string |
| http://purl.uniprot.org/citations/36056105 | http://purl.uniprot.org/core/author | "Dighe N.M."xsd:string |
| http://purl.uniprot.org/citations/36056105 | http://purl.uniprot.org/core/date | "2023"xsd:gYear |
| http://purl.uniprot.org/citations/36056105 | http://purl.uniprot.org/core/name | "Neuropsychopharmacology"xsd:string |
| http://purl.uniprot.org/citations/36056105 | http://purl.uniprot.org/core/pages | "1108-1117"xsd:string |
| http://purl.uniprot.org/citations/36056105 | http://purl.uniprot.org/core/title | "GluN2B inhibition confers resilience against long-term cocaine-induced neurocognitive sequelae."xsd:string |
| http://purl.uniprot.org/citations/36056105 | http://purl.uniprot.org/core/volume | "48"xsd:string |
| http://purl.uniprot.org/citations/36056105 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/36056105 |
| http://purl.uniprot.org/citations/36056105 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/36056105 |
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| http://purl.uniprot.org/uniprot/#_G3X9V4-mappedCitation-36056105 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/36056105 |
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