{"doi":"10.1111/acer.70055","title":"Diet, diet access, and metabolic physiology as critically understudied factors in rodent models of alcohol intake: A commentary on Emous et al. (2025)","abstract":"Alcohol use disorder (AUD) is a complex disease encompassing a spectrum of behavioral and physiological dysfunctions that stem from disruptions at the cellular, genomic, and organ levels. Animal models have been used extensively to study potential mechanisms by which alcohol exposure induces these disruptions, but treatments that target these identified mechanisms have had limited clinical efficacy. One reason for the lack of translation may be the numerous hidden variables that are inherent in any animal model (Butler-Struben et al., 2022). In particular for AUD models, diet and diet/alcohol impacts on whole-animal physiology are often overlooked as a potential variable in the alteration of alcohol-related behaviors and outcomes. The impact of diet on alcohol intake in rodent models has been examined with a number of different approaches. Studies as early as the 1950s examined various diet formulations and diets with distinct composition deficits and found that diet types can significantly alter alcohol intake in mouse models in strain-specific manners (Mirone, 1957) and that diet composition, such as fats, proteins, and carbohydrates, can significantly impact alcohol intake in rodent models (Forsander, 1998). However, more recent studies have shown that different “standard” chow diets from current commercial laboratory diet sources can differentially impact alcohol intake in mouse models even though these diets had similar composition (Quadir et al., 2020). Additionally, studies indicate maintenance on ketogenic diets (Blanco-Gandía et al., 2021) and high-fat diets (Gelineau et al., 2017) can reduce alcohol intake. These effects can occur through a variety of mechanisms, including altered stress hormones (Flores-Bonilla & Richardson, 2020), disrupted reward processing (Siciliano et al., 2018), altered microbiome (Patel et al., 2022), inflammation (Vore & Deak, 2022), and disrupted vagal signaling (Keller et al., 2022). It should be noted that the impact of high-fat diets on alcohol intake may be dependent on the timing of diet consumption in relation to alcohol intake. For instance, a high-fat diet period in adolescence can increase future alcohol intake in mice (Blanco-Gandía et al., 2018), while other work described how limited access to a high-fat diet interspersed with alcohol drinking sessions can increase alcohol intake in adult male mice (Coker et al., 2020). Overall, these findings indicate overlapping mechanisms of food and alcohol intake that are dependent on timing and type of diets and the alcohol intake model and mechanisms being assessed. However, none of these studies examined alcohol intake with the critical variable of the absence or presence of any food during the intake sessions themselves. The study by Emous et al. (2025) fills this gap by directly examining the role of standard chow availability within alcohol intake sessions in male and female mice. This was done in C57Bl/6 and Swiss–Webster mice, further allowing for cross-strain comparisons. Overall, this study found that the presence of food increased alcohol and water intake in C57Bl/6 mice while it mainly enhanced water intake in Swiss–Webster mice. It should be noted that water intake in early sessions was highest in both C57Bl/6 and Swiss–Webster mice with food availability, while mice that were initially food deprived in early sessions and switched to food availability in later sessions increased their fluid intake, suggesting the availability of food may enhance overall fluid intake. It is intriguing that food availability decreased alcohol intake in male Swiss–Webster mice, suggesting that there may be a balance of intake behaviors toward food, water, and alcohol that could be regulated by central and peripheral pathways that may be strain-specific, similar to strain-specific differences in alcohol preference. This study does have a few limitations and raises interesting questions regarding the role of caloric value in alcohol intake under foo","journal":"Alcohol Clinical and Experimental Research","year":2025,"id":552432,"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":0.9554,"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":454715,"name":"A. Hajnal","orcid":"0000-0001-7297-7134","position":1,"is_corresponding":false},{"id":320868,"name":"Yuval Silberman","orcid":"0000-0002-4694-4053","position":0,"is_corresponding":true}],"reference_count":21,"raw_metadata":null,"created_at":"2026-07-19T02:54:33.203144Z","pmid":"40251985","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":[]}