{"doi":"10.1111/adb.13107","title":"Neurobeachin, a promising target for use in the treatment of alcohol use disorder","abstract":"Hazardous, heavy drinking increases risk for developing alcohol use disorder (AUD), which affects ~7% of adult Americans. Thus, understanding the molecular mechanisms promoting risk for heavy drinking is essential to developing more effective AUD pharmacotherapies than those currently approved by the FDA. Using genome-wide bisulfate sequencing, we identified DNA methylation (DNAm) signals within the nucleus accumbens core (NAcC) that differentiate nonheavy and heavy ethanol-drinking rhesus macaques. One differentially DNAm region (D-DMR) located within the gene neurobeachin (NBEA), which promotes synaptic membrane protein trafficking, was hypermethylated in heavy drinking macaques. A parallel study identified a similar NBEA D-DMR in human NAcC that distinguished alcoholic and nonalcoholic individuals. To investigate the role of NBEA in heavy ethanol drinking, we engineered a viral vector carrying a short hairpin RNA (shRNA) to reduce the expression of NBEA. Using two murine models of ethanol consumption: 4 days of drinking-in-the-dark and 4 weeks of chronic intermittent access, the knockdown of NBEA expression did not alter average ethanol consumption in either model. However, it did lead to a significant increase in the ethanol preference ratio. Following withdrawal, whole-cell patch clamp electrophysiological experiments revealed that Nbea knockdown led to an increase in spontaneous excitatory postsynaptic current amplitude with no alteration in spontaneous inhibitory postsynaptic currents, suggesting a specific role of NBEA in trafficking of glutamatergic receptors. Together, our findings suggest that NBEA could be targeted to modulate the preference for alcohol use.","journal":"Addiction Biology","year":2021,"id":205576,"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":0.9553,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":286438,"name":"Carlos F. Aylwin","orcid":"0000-0003-2143-3641","position":1,"is_corresponding":false},{"id":766381,"name":"Timothy L. Carlson","orcid":null,"position":2,"is_corresponding":false},{"id":488261,"name":"Matthew M. Ford","orcid":"0000-0002-1204-1980","position":3,"is_corresponding":false},{"id":788878,"name":"Houda Mesnaoui","orcid":"0000-0002-1690-3568","position":4,"is_corresponding":false},{"id":277685,"name":"Alejandro Lomniczi","orcid":"0000-0003-4535-0103","position":5,"is_corresponding":false},{"id":246461,"name":"Betsy Ferguson","orcid":"0000-0002-6992-3538","position":6,"is_corresponding":false},{"id":719632,"name":"Rita Cervera‐Juanes","orcid":"0000-0002-0001-3640","position":7,"is_corresponding":false},{"id":488260,"name":"Verginia C. Cuzon Carlson","orcid":"0000-0002-8858-3241","position":0,"is_corresponding":true}],"reference_count":54,"raw_metadata":null,"created_at":"2026-07-18T23:51:33.996102Z","pmid":"34699111","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":[]}