{"doi":"10.3389/adar.2024.12528","title":"Effects of repeated alcohol abstinence on within-subject prefrontal cortical gene expression in rhesus macaques","abstract":"Male rhesus monkeys ( n = 24) had a biopsy of prefrontal cortical area 46 prior to chronic ethanol self-administration ( n = 17) or caloric control ( n = 7). Fourteen months of daily self-administration (water vs. 4% alcohol, 22 h access/day termed “open-access”) was followed by two cycles of prolonged abstinence (5 weeks) each followed by 3 months of open-access alcohol and a final abstinence followed by necropsy. At necropsy, a biopsy of Area 46, contralateral to the original biopsy, was obtained. Gene expression data (RNA-Seq) were collected comparing biopsy/necropsy samples. Monkeys were categorized by drinking status during the final post-abstinent drinking phase as light (LD), binge (BD), heavy (HD) and very heavy (VHD drinkers). Comparing pre-ethanol to post-abstinent biopsies, four animals that converted from HD to VHD status had significant ontology enrichments in downregulated genes (necropsy minus biopsy n = 286) that included immune response (FDR < 9 × 10 −7 ) and plasma membrane changes (FDR < 1 × 10 −7 ). Genes in the immune response category included IL16 and 18 , CCR1 , B2M , TLR3 , 6 and 7 , SP2 and CX3CR1 . Upregulated genes ( N = 388) were particularly enriched in genes associated with the negative regulation of MAP kinase activity (FDR < 3 × 10 −5 ), including DUSP 1 , 4 , 5 , 6 and 18 , SPRY 2 , 3 , and 4 , SPRED2 , BMP4 and RGS2 . Overall, these data illustrate the power of the NHP model and the within-subject design of genomic changes due to alcohol and suggest new targets for treating severe escalated drinking following repeated alcohol abstinence attempts.","journal":"Advances in Drug and Alcohol Research","year":2024,"id":455746,"datarank":0.29188652235829704,"base_score":1.9459101490553132,"endowment":1.9459101490553132,"self_citation_contribution":0.29188652235829704,"citation_network_contribution":0.0,"self_endowment_contribution":0.29188652235829704,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":6,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9101,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":314329,"name":"Lina Gao","orcid":"0000-0001-9382-0419","position":1,"is_corresponding":false},{"id":307548,"name":"Suzanne S. Fei","orcid":"0000-0002-9688-2890","position":2,"is_corresponding":false},{"id":724506,"name":"Karina Ray","orcid":"0000-0001-5077-3747","position":3,"is_corresponding":false},{"id":647700,"name":"Katinka A. Vigh‐Conrad","orcid":"0000-0002-8222-7537","position":4,"is_corresponding":false},{"id":533539,"name":"Tamara J. Phillips","orcid":"0000-0002-7350-6323","position":5,"is_corresponding":false},{"id":307549,"name":"Robert P. Searles","orcid":"0000-0002-0378-2322","position":6,"is_corresponding":false},{"id":719632,"name":"Rita Cervera‐Juanes","orcid":"0000-0002-0001-3640","position":7,"is_corresponding":false},{"id":1279844,"name":"Rupak Khadka","orcid":"0009-0003-7838-450X","position":8,"is_corresponding":false},{"id":766381,"name":"Timothy L. Carlson","orcid":null,"position":9,"is_corresponding":false},{"id":487856,"name":"Steven W. Gonzales","orcid":null,"position":10,"is_corresponding":false},{"id":369964,"name":"Natali Newman","orcid":"0000-0003-3818-9673","position":11,"is_corresponding":false},{"id":185577,"name":"Kathleen A. Grant","orcid":"0000-0002-0380-7219","position":12,"is_corresponding":false},{"id":610425,"name":"Robert Hitzemann","orcid":null,"position":0,"is_corresponding":true}],"reference_count":72,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:03:22.974789Z","pmid":"38737578","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":[]}