{"doi":"10.1159/000054522","title":"Dopaminergic Agonists Normalize Elevated Hypothalamic Neuropeptide Y and Corticotropin-Releasing Hormone, Body Weight Gain, and Hyperglycemia in ob/ob Mice","abstract":"Hypothalamic neuropeptide Y (NPY) and corticotropin-releasing hormone (CRH) influence feeding and levels of plasma glucose, insulin, free fatty acids, and triglycerides. Treatment of genetically obese, ob/ob mice, with dopamine receptor D<sub>1</sub>/D<sub>2</sub> agonists normalizes hyperphagia, body weight gain, hyperglycemia, and hyperlipidemia. We therefore examined whether levels of NPY and CRH immunoreactivity in discrete hypothalamic nuclei are altered in ob/ob mice, and whether dopaminergic treatment reverses this alteration. Female ob/ob mice were treated daily at 1 h after light onset with the D<sub>1</sub>/D<sub>2</sub> agonists, SKF-38393 (20 mg/kg) and bromocriptine (15 mg/kg), respectively or vehicle for 2 weeks. Such treatment, while normalizing body weight gain and hyperglycemia, also significantly reduced elevated NPY immunoreactivity in the suprachiasmatic (by 39%), intergeniculate (by 43%), paraventricular (PVN; by 31%), and arcuate (by 41%) nuclei in obese mice to levels observed in lean mice. This treatment also caused a 45–50% decline in levels of CRH in the PVN and dorsomedial hypothalamus compared to obese controls to levels observed in lean mice. Taken together, these findings suggest that dopaminergic D<sub>1</sub>/D<sub>2</sub> receptor coactivation may improve hyperphagia, hyperglycemia, and obesity in the ob/ob mouse, in part, by normalizing elevated levels of both NPY and CRH.","journal":"Neuroendocrinology","year":2000,"id":589008,"datarank":7.366295715918421,"base_score":5.017279836814924,"endowment":5.017279836814924,"self_citation_contribution":0.7525919755222388,"citation_network_contribution":6.613703740396182,"self_endowment_contribution":0.7525919755222388,"citer_contribution":6.613703740396182,"corpus_percentile":null,"corpus_rank":null,"citation_count":150,"citer_count":136,"citers_with_citation_signal":126,"citers_with_endowment":126,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1506967,"name":"Anthony H. Cincotta","orcid":null,"position":1,"is_corresponding":false},{"id":1506966,"name":"Keshavan G. Bina","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Dopaminergic Agonists Normalize Elevated Hypothalamic Neuropeptide Y and Corticotropin-Releasing Hormone, Body Weight Gain, and Hyperglycemia in ob/ob Mice","abstract":"Hypothalamic neuropeptide Y (NPY) and corticotropin-releasing hormone (CRH) influence feeding and levels of plasma glucose, insulin, free fatty acids, and triglycerides. Treatment of genetically obese, ob/ob mice, with dopamine receptor D<sub>1</sub>/D<sub>2</sub> agonists normalizes hyperphagia, body weight gain, hyperglycemia, and hyperlipidemia. We therefore examined whether levels of NPY and CRH immunoreactivity in discrete hypothalamic nuclei are altered in ob/ob mice, and whether dopaminergic treatment reverses this alteration. Female ob/ob mice were treated daily at 1 h after light onset with the D<sub>1</sub>/D<sub>2</sub> agonists, SKF-38393 (20 mg/kg) and bromocriptine (15 mg/kg), respectively or vehicle for 2 weeks. Such treatment, while normalizing body weight gain and hyperglycemia, also significantly reduced elevated NPY immunoreactivity in the suprachiasmatic (by 39%), intergeniculate (by 43%), paraventricular (PVN; by 31%), and arcuate (by 41%) nuclei in obese mice to levels observed in lean mice. This treatment also caused a 45–50% decline in levels of CRH in the PVN and dorsomedial hypothalamus compared to obese controls to levels observed in lean mice. Taken together, these findings suggest that dopaminergic D<sub>1</sub>/D<sub>2</sub> receptor coactivation may improve hyperphagia, hyperglycemia, and obesity in the ob/ob mouse, in part, by normalizing elevated levels of both NPY and CRH.","is_dataset_classified":null,"base_score":5.017279836814924,"endowment":5.017279836814924,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"10644901","pmcid":null,"openalex_id":"https://openalex.org/W1972779667","authors":[],"funders":[],"total_grants":0,"fwci":2.9659,"citation_percentile":0.92462187,"influential_citations":0,"citation_trend":[{"year":2012,"count":2},{"year":2013,"count":5},{"year":2014,"count":6},{"year":2015,"count":7},{"year":2016,"count":3},{"year":2017,"count":7},{"year":2018,"count":2},{"year":2019,"count":4},{"year":2020,"count":8},{"year":2021,"count":7},{"year":2022,"count":1},{"year":2023,"count":3},{"year":2024,"count":5},{"year":2025,"count":2}],"oa_status":"closed","license":"https://www.karger.com/Services/SiteLicenses","oa_locations":[{"url":"https://www.karger.com/Article/Pdf/54522","host_type":"publisher"},{"url":"https://doi.org/10.1159/000054522","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/10644901","host_type":"repository"}],"fields_of_study":["Regulation of Appetite and Obesity","Stress Responses and Cortisol","Adipose Tissue and Metabolism"],"mesh_terms":["Animals","Arcuate Nucleus of Hypothalamus","Blood Glucose","Corticotropin-Releasing Hormone","Dorsomedial Hypothalamic Nucleus","Eating","Female","Hyperglycemia","Hypothalamus","Mice, Inbred C57BL","Mice, Obese","Neuropeptide Y","Obesity","Paraventricular Hypothalamic Nucleus","RNA, Messenger","Suprachiasmatic Nucleus","Weight Gain","Gene Expression","Receptors, Dopamine D1","Mice","Dopamine D2 Receptor Antagonists"],"keywords":["Endocrinology","Internal medicine","Neuropeptide Y receptor","Corticotropin-releasing hormone","Neuropeptide","Dopaminergic","Hypothalamus","Medicine","Proopiomelanocortin","Hormone","Dopamine","Receptor"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-23T11:38:28.150143Z","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":[]}