{"doi":"10.1126/science.adk6742","title":"Drugs of abuse hijack a mesolimbic pathway that processes homeostatic need","abstract":"Drugs of abuse are thought to promote addiction in part by “hijacking” brain reward systems, but the underlying mechanisms remain undefined. Using whole-brain FOS mapping and in vivo single-neuron calcium imaging, we found that drugs of abuse augment dopaminoceptive ensemble activity in the nucleus accumbens (NAc) and disorganize overlapping ensemble responses to natural rewards in a cell type–specific manner. Combining FOS-Seq, CRISPR-perturbation, and single-nucleus RNA sequencing, we identified Rheb as a molecular substrate that regulates cell type–specific signal transduction in NAc while enabling drugs to suppress natural reward consumption. Mapping NAc-projecting regions activated by drugs of abuse revealed input-specific effects on natural reward consumption. These findings characterize the dynamic, molecular and circuit basis of a common reward pathway, wherein drugs of abuse interfere with the fulfillment of innate needs.","journal":"Science","year":2024,"id":418066,"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":56,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9524,"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":136089,"name":"Caleb J Browne","orcid":"0000-0003-0089-5433","position":1,"is_corresponding":false},{"id":263862,"name":"Tobias Nöbauer","orcid":"0000-0001-9959-4539","position":2,"is_corresponding":false},{"id":263863,"name":"Alipasha Vaziri","orcid":"0000-0001-8346-7551","position":3,"is_corresponding":false},{"id":470094,"name":"Jeffrey M. Friedman","orcid":"0000-0003-2152-0868","position":4,"is_corresponding":false},{"id":196103,"name":"Eric J. Nestler","orcid":"0000-0002-7905-2000","position":5,"is_corresponding":false},{"id":891701,"name":"Bowen Tan","orcid":"0000-0003-3036-2881","position":0,"is_corresponding":true}],"reference_count":105,"raw_metadata":null,"created_at":"2026-07-19T01:57:02.483590Z","pmid":"38669575","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":[]}