{"doi":"10.1101/2025.05.21.655393","title":"AMPA receptor activation within the prelimbic cortex is necessary for incubated cocaine-craving","abstract":"The incubation of craving is a behavioral phenomenon in which cue-elicited craving increases during a period of drug abstinence. Incubated cocaine-craving is associated with increased extracellular glutamate within the medial prefrontal cortex (mPFC) and this release, particularly within the prelimbic (PL) subregion, is necessary for incubated cocaine-craving. A potential candidate mediating these incubation-driving effects of glutamate release within the PL are alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs). To investigate the role of mPFC AMPARs in incubated craving, male and female Sprague-Dawley rats were trained to self-administer cocaine for 6 h/day for 10 consecutive days. Either during early or later withdrawal, rats were infused intra-PL with the AMPAR antagonist NBQX (0 or 1 μg/0.5 μl per side), followed by 30-min tests for cue-reinforced responding. Immunoblotting was also conducted to relate the expression of incubated cocaine- and sucrose-craving to AMPAR subunit expression within mPFC subregions. Intra-PL NBQX blocked incubated craving expressed in late, but not early, withdrawal. No incubation-related changes in AMPAR subunit expression were detected within the PL or IL of rats of either sex and no estrus-associated changes in subunit expression were detected in female rats exhibiting incubated cocaine-craving. In contrast, elevated GluA1 expression was observed within the IL of male rats exhibiting an incubation of sucrose-craving. Together, these findings indicate a necessary role for AMPARs within the PL in driving incubated cocaine-craving and suggest that AMPARs located within the IL may be involved also in sucrose-craving selectively in males.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":558012,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9489,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1458463,"name":"Mirette G. Tadros","orcid":null,"position":1,"is_corresponding":false},{"id":1079103,"name":"Hoa H.T. Doan","orcid":null,"position":2,"is_corresponding":false},{"id":1458464,"name":"Sophie Vo","orcid":null,"position":3,"is_corresponding":false},{"id":1458465,"name":"Sanil R. Chaudhari","orcid":null,"position":4,"is_corresponding":false},{"id":1079102,"name":"Taylor L. Li","orcid":null,"position":5,"is_corresponding":false},{"id":991191,"name":"Peter James","orcid":"0000-0002-6373-5704","position":6,"is_corresponding":false},{"id":1458466,"name":"Audrey Y. Na","orcid":null,"position":7,"is_corresponding":false},{"id":1458031,"name":"Fernando Cano","orcid":"0000-0002-9589-8671","position":8,"is_corresponding":false},{"id":542602,"name":"Tod E. Kippin","orcid":"0000-0003-3216-8863","position":9,"is_corresponding":false},{"id":375684,"name":"Karen K. Szumlinski","orcid":"0000-0003-1078-1077","position":10,"is_corresponding":false},{"id":833631,"name":"Laura L. Huerta Sanchez","orcid":"0009-0001-0870-8252","position":0,"is_corresponding":true}],"reference_count":53,"raw_metadata":null,"created_at":"2026-07-19T02:55:21.727661Z","pmid":"40475553","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}