title: The effects of reboxetine treatment on depression-like behavior, brain neurotrophins, and ERK expression in rats exposed to chronic mild stress.
abstract: Chronic mild stress (CMS) in rats is an established rodent depression model. Antidepressants attenuate the depression-like symptoms and prevent the biochemical changes caused by stress. In the present study, we examined the effect of CMS and the selective norepinephrine reuptake inhibitor (NRI) reboxetine (REB) treatment on behavioral parameters in rats and on hippocampal and cortical neurotrophic factors. Male Sprague Dawley rats were exposed for 5 weeks to a variety of mild stressors. REB (5 mg/kg/i.p.) was daily injected to half of the stressed and unstressed groups. Animal behavior following CMS was tested using the Morris Water Maze (MWM) cognitive paradigm and by monitoring sucrose intake and weight gain. After 5 weeks of CMS, stressed rats showed decreased sucrose intake, and REB treatment normalized this decrease. CMS reduced hippocampal brain-derived neurotrophic factor (BDNF) levels, and REB treatment reversed this alteration and increased BDNF receptor (TrkB) levels. REB elevated hippocampal extracellular signal-regulated kinase (ERK) phosphorylation of both stressed and unstressed rats. In conclusion, our study shows that BDNF, its receptor TrkB, and ERK participate in the neurobiological response to chronic stress and in the molecular and cellular activities of REB in the hippocampus.
authors.affiliation: Laboratory of Biological Psychiatry, Felsenstein Medical Research Center and Sackler Faculty of Medicine, Tel-Aviv University, Petach Tikva 49100, Israel.
authors.forename: Maya
authors.initials: M
authors.lastname: First
authors.forename: Irit
authors.initials: I
authors.lastname: Gil-Ad
authors.forename: Michal
authors.initials: M
authors.lastname: Taler
authors.forename: Igor
authors.initials: I
authors.lastname: Tarasenko
authors.forename: Nurit
authors.initials: N
authors.lastname: Novak
authors.forename: Abraham
authors.initials: A
authors.lastname: Weizman
mesh_terms: D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001921:Brain / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D003866:Depressive Disorder / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D019422:Dietary Sucrose; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism*; D005518:Food Preferences / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D009025:Morpholines / Q000494:pharmacology / Q000627:therapeutic use*; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077593:Reboxetine; D020813:Receptor, trkB / Q000235:genetics / Q000378:metabolism; D013315:Stress, Psychological / Q000150:complications*; D015430:Weight Gain / Q000187:drug effects
chemical_list: D018759:Adrenergic Uptake Inhibitors; D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor; D019422:Dietary Sucrose; D009025:Morpholines; D000077593:Reboxetine; D020813:Receptor, trkB; D048049:Extracellular Signal-Regulated MAP Kinases