{"doi":"10.1101/2022.09.08.506493","title":"Cocaine addiction-like behaviors are associated with long-term changes in gene regulation, energy metabolism, and GABAergic inhibition within the amygdala","abstract":"Abstract The amygdala processes positive and negative valence and contributes to the development of addiction, but the underlying cell type-specific gene regulatory programs are unknown. We generated an atlas of single nucleus gene expression and chromatin accessibility in the amygdala of outbred rats with low and high cocaine addiction-like behaviors following prolonged abstinence. Between rats with different addiction indexes, we identified thousands of cell type-specific differentially expressed genes enriched for energy metabolism-related pathways that are known to affect synaptic transmission and action potentials. Rats with high addiction-like behaviors showed enhanced GABAergic transmission in the amygdala, which, along with relapse-like behaviors, were reversed by inhibition of Glyoxalase 1, which metabolizes the GABA A receptor agonist methylglyoxal. Finally, we identified thousands of cell type-specific chromatin accessible sites and transcription factor (TF) motifs where accessibility was associated with addiction index, most notably at motifs for pioneer TFs in the Fox, Sox, helix-loop-helix, and AP1 families.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":300417,"datarank":0.22348986127672207,"base_score":1.3862943611198906,"endowment":1.3862943611198906,"self_citation_contribution":0.20794415416798362,"citation_network_contribution":0.015545707108738467,"self_endowment_contribution":0.20794415416798362,"citer_contribution":0.015545707108738467,"corpus_percentile":37.61120136149145,"corpus_rank":8066,"citation_count":3,"citer_count":1,"citers_with_citation_signal":1,"citers_with_endowment":1,"datacite_reuse_total":0,"is_dataset":true,"is_dataset_confidence":0.5234,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":329614,"name":"Giordano de Guglielmo","orcid":"0000-0002-4782-7430","position":1,"is_corresponding":false},{"id":991420,"name":"Aaron J. Ho","orcid":null,"position":2,"is_corresponding":false},{"id":329615,"name":"Marsida Kallupi","orcid":"0000-0002-8688-709X","position":3,"is_corresponding":false},{"id":990894,"name":"Narayan Pokhrel","orcid":"0000-0002-4753-1621","position":4,"is_corresponding":false},{"id":43060,"name":"Hairi Li","orcid":null,"position":5,"is_corresponding":false},{"id":813003,"name":"Apurva S. Chitre","orcid":"0000-0003-1709-9214","position":6,"is_corresponding":false},{"id":317100,"name":"Daniel Munro","orcid":"0000-0002-0724-218X","position":7,"is_corresponding":false},{"id":29313,"name":"Pejman Mohammadi","orcid":"0000-0003-4457-8552","position":8,"is_corresponding":false},{"id":812995,"name":"Lieselot L. G. Carrette","orcid":"0000-0002-5217-2774","position":9,"is_corresponding":false},{"id":329618,"name":"Olivier George","orcid":"0000-0002-3700-5003","position":10,"is_corresponding":false},{"id":230002,"name":"Abraham A. Palmer","orcid":"0000-0003-3634-0747","position":11,"is_corresponding":false},{"id":43077,"name":"Graham McVicker","orcid":"0000-0003-0991-0951","position":12,"is_corresponding":false},{"id":583612,"name":"Francesca Telese","orcid":"0000-0003-3877-0628","position":13,"is_corresponding":false},{"id":58765,"name":"Jessica Zhou","orcid":"0000-0002-4131-0756","position":0,"is_corresponding":true}],"reference_count":133,"raw_metadata":null,"created_at":"2026-07-19T00:31:53.559757Z","pmid":null,"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":[]}