title: Animal Models of Depression and Drug Delivery with Food as an Effective Dosing Method: Evidences from Studies with Celecoxib and Dicholine Succinate.
abstract: Multiple models of human neuropsychiatric pathologies have been generated during the last decades which frequently use chronic dosing. Unfortunately, some drug administration methods may result in undesirable effects creating analysis confounds hampering model validity and preclinical assay outcomes. Here, automated analysis of floating behaviour, a sign of a depressive-like state, revealed that mice, subjected to a three-week intraperitoneal injection regimen, had increased floating. In order to probe an alternative dosing design that would preclude this effect, we studied the efficacy of a low dose of the antidepressant imipramine (7 mg/kg/day) delivered via food pellets. Antidepressant action for this treatment was found while no other behavioural effects were observed. We further investigated the potential efficacy of chronic dosing via food pellets by testing the antidepressant activity of new drug candidates, celecoxib (30 mg/kg/day) and dicholine succinate (50 mg/kg/day), against standard antidepressants, imipramine (7 mg/kg/day) and citalopram (15 mg/kg/day), utilizing the forced swim and tail suspension tests. Antidepressant effects of these compounds were found in both assays. Thus, chronic dosing via food pellets is efficacious in small rodents, even with a low drug dose design, and can prevail against potential confounds in translational research within depression models applicable to adverse chronic invasive pharmacotherapies.
authors.affiliation: Department of Neuroscience, School for Mental Health and Neuroscience, Maastricht University, Universiteitssingel 40, 6200 MD Maastricht, Netherlands ; CBA, Faculdade de Ciencias, Universidade de Lisboa, Campo Grande, 1749-016 Lisboa, Portugal ; Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Rua da Junqueira 100, 1349-008 Lisboa, Portugal.
authors.forename: João P
authors.initials: JP
authors.lastname: Costa-Nunes
authors.affiliation: INSERM U1119, Université de Strasbourg, Bâtiment 3 de la Faculté de Médecine, 11 rue Humann, 67000 Strasbourg, France.
authors.forename: Brandon H
authors.initials: BH
authors.lastname: Cline
authors.affiliation: CBA, Faculdade de Ciencias, Universidade de Lisboa, Campo Grande, 1749-016 Lisboa, Portugal ; Chronic Diseases Research Center, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Campo Mártires da Pátria 130, 1169-056 Lisboa, Portugal.
authors.forename: Margarida
authors.initials: M
authors.lastname: Araújo-Correia
authors.affiliation: CBA, Faculdade de Ciencias, Universidade de Lisboa, Campo Grande, 1749-016 Lisboa, Portugal ; Faculdade de Medicina Veterinária, Universidade Técnica de Lisboa, Avenida da Universidade Técnica, 1300-477 Lisboa, Portugal.
authors.forename: Andreia
authors.initials: A
authors.lastname: Valença
authors.affiliation: Institute of General Pathology and Pathophysiology, Russian Academy of Medical Sciences, Baltiyskaya 8, Moscow 125315, Russia ; Institute of Physiologically Active Compounds, Russian Academy of Sciences, Severnii proesd 1, Chernogolovka, Moscow Region 142432, Russia.
authors.forename: Natalyia
authors.initials: N
authors.lastname: Markova
authors.affiliation: Anokhin Institute of Normal Physiology, Russian Academy of Medical Sciences, Baltiyskaya 8, Moscow 125315, Russia.
authors.forename: Oleg
authors.initials: O
authors.lastname: Dolgov
authors.affiliation: Institute of General Pathology and Pathophysiology, Russian Academy of Medical Sciences, Baltiyskaya 8, Moscow 125315, Russia.
authors.forename: Aslan
authors.initials: A
authors.lastname: Kubatiev
authors.affiliation: Division of Cardiology, University Hospital Magdeburg, Leipziger Strasse 44, 39120 Magdeburg, Germany.
authors.forename: Naira
authors.initials: N
authors.lastname: Yeritsyan
authors.affiliation: Department of Neuroscience, School for Mental Health and Neuroscience, Maastricht University, Universiteitssingel 40, 6200 MD Maastricht, Netherlands.
authors.forename: Harry W M
authors.initials: HW
authors.lastname: Steinbusch
authors.affiliation: Department of Neuroscience, School for Mental Health and Neuroscience, Maastricht University, Universiteitssingel 40, 6200 MD Maastricht, Netherlands ; Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Rua da Junqueira 100, 1349-008 Lisboa, Portugal ; Institute of Physiologically Active Compounds, Russian Academy of Sciences, Severnii proesd 1, Chernogolovka, Moscow Region 142432, Russia.
authors.forename: Tatyana
authors.identifier: 0000-0001-9937-5600
authors.initials: T
authors.lastname: Strekalova
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage*; D001522:Behavior, Animal / Q000187:drug effects; D000068579:Celecoxib / Q000008:administration & dosage*; D003866:Depressive Disorder / Q000188:drug therapy* / Q000503:physiopathology; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D006801:Humans; D051379:Mice; D019802:Succinic Acid / Q000008:administration & dosage*; D013550:Swimming
chemical_list: D000928:Antidepressive Agents; D019802:Succinic Acid; D000068579:Celecoxib