title: Peripheral proinflammatory markers associated with ketamine response in a preclinical model of antidepressant-resistance.
abstract: Ketamine, N-methyl-d-aspartate (NMDA) receptor antagonist and anti-inflammatory agent, has rapid therapeutic effects in a subset of patients with more intractable forms of depression. Irregular proinflammatory cytokine and acute-reactive protein levels have been reported in clinical and preclinical depression research. We explored the association between the rapid antidepressant-like effects of ketamine and peripheral proinflammatory profile in a model of antidepressant-resistance. Male Wistar rats were pre-treated with ACTH-(1-24) 100μg/d or saline (0.9%) for 14d. Antidepressant-like effects were assessed with the forced swim test (FST). Ketamine (10mg/kg) significantly reduced immobility duration in saline-pretreated control animals. In contrast, a divergent response was observed in ACTH-pretreated antidepressant resistant animals, with 50% responders and 50% non-responders. Plasma samples were analyzed via enzyme-linked immunosorbent assay (ELISA) for interleukin 6 (IL-6), tumour necrosis factor alpha (TNFα) and C-reactive protein (CRP). Levels of CRP and TNFα differentiated ketamine responders and non-responders.
authors.affiliation: Department of Psychiatry and Psychology, Mayo Clinic, 200 First Street Southwest, Rochester MN 55905, United States; School of Psychology, Deakin University, 221 Burwood Highway, Burwood VIC 3125, Australia.
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Walker
authors.affiliation: Department of Psychiatry and Psychology, Mayo Clinic, 200 First Street Southwest, Rochester MN 55905, United States; University of San Diego, 5998 Alcalá Park, San Diego CA 92110, United States.
authors.forename: Brittany M
authors.initials: BM
authors.lastname: Foley
authors.affiliation: Department of Psychiatry and Psychology, Mayo Clinic, 200 First Street Southwest, Rochester MN 55905, United States.
authors.forename: Shari L
authors.initials: SL
authors.lastname: Sutor
authors.affiliation: School of Psychology, Deakin University, 221 Burwood Highway, Burwood VIC 3125, Australia.
authors.forename: Jane A
authors.initials: JA
authors.lastname: McGillivray
authors.affiliation: Department of Psychiatry and Psychology, Mayo Clinic, 200 First Street Southwest, Rochester MN 55905, United States.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Frye
authors.affiliation: Department of Psychiatry and Psychology, Mayo Clinic, 200 First Street Southwest, Rochester MN 55905, United States; School of Psychology, Deakin University, 221 Burwood Highway, Burwood VIC 3125, Australia; Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, 200 First Street Southwest, Rochester MN 55905, United States; Department of Psychiatry, University of Minnesota, Minneapolis, MN 55455, United States. Electronic address: tye.susannah@mayo.edu.
authors.forename: Susannah J
authors.initials: SJ
authors.lastname: Tye
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002097:C-Reactive Protein / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism*; D003863:Depression / Q000188:drug therapy* / Q000378:metabolism*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004797:Enzyme-Linked Immunosorbent Assay; D005106:Exploratory Behavior / Q000187:drug effects; D046353:Immobility Response, Tonic / Q000187:drug effects; D007649:Ketamine / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013550:Swimming
chemical_list: D000928:Antidepressive Agents; D016207:Cytokines; D007649:Ketamine; D000324:Adrenocorticotropic Hormone; D002097:C-Reactive Protein
keywords: Adrenocorticotropic hormone (ACTH); Animal model; C-reactive protein (CRP); Cytokine; Ketamine; Treatment-resistant depression (TRD)