{"doi":"10.1101/2021.01.04.425260","title":"HIV-1-induced apathy: Mitigation by the gut metabolite, S-Equol","abstract":"ABSTRACT The persistence of motivational alterations, including apathy, in older HIV-1 seropositive individuals, despite treatment with combination antiretroviral therapy, necessitates the development of innovative adjunctive therapeutics. S-Equol (SE), a selective estrogen receptor β agonist, has been implicated as a neuroprotective and/or neurorestorative therapeutic for HIV-1 associated neurocognitive disorders (HAND); its therapeutic utility for apathy, however, has yet to be systematically evaluated. Thus, beginning at approximately seven to nine months of age, HIV-1 transgenic (Tg) and control animals were treated with either a daily oral dose of SE (0.2 mg) or vehicle and assessed in a series of tasks to evaluate goal-directed behavior. First, at the genotypic level, apathetic behavior in older HIV-1 Tg rats treated with vehicle was characterized by a diminished reinforcing efficacy of, and sensitivity to, sucrose and enhanced drug seeking for cocaine relative to control animals treated with vehicle. Second, treatment with SE ameliorated alterations in goal-directed behaviors and reduced drug seeking behavior in HIV-1 Tg rats. Following a history of cocaine self-administration, HIV-1 Tg animals treated with vehicle exhibited prominent decreases in dendritic branching and a shift towards longer dendritic spines with decreased head diameter; synaptic dysfunction that was partially restored by SE treatment. Taken together, SE restored motivated behavior in the HIV-1 Tg rat, expanding the potential clinical utility of SE to include both neurocognitive and affective alterations.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":220041,"datarank":0.11664250941680801,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.012670432332816204,"self_endowment_contribution":0.10397207708399181,"citer_contribution":0.012670432332816204,"corpus_percentile":null,"corpus_rank":null,"citation_count":1,"citer_count":1,"citers_with_citation_signal":1,"citers_with_endowment":1,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9548,"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":771192,"name":"Sarah J. Bertrand","orcid":null,"position":1,"is_corresponding":false},{"id":576865,"name":"Jessica M. Illenberger","orcid":"0000-0002-1841-9139","position":2,"is_corresponding":false},{"id":588985,"name":"Steven B. Harrod","orcid":"0000-0002-4313-3503","position":3,"is_corresponding":false},{"id":576866,"name":"Charles F. Mactutus","orcid":"0000-0002-6508-1329","position":4,"is_corresponding":false},{"id":576867,"name":"Rosemarie M. Booze","orcid":"0000-0003-3908-8313","position":5,"is_corresponding":false},{"id":576864,"name":"Kristen A. McLaurin","orcid":"0000-0001-7816-1806","position":0,"is_corresponding":true}],"reference_count":83,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-18T23:53:42.928212Z","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":[]}