title: Antidepressant effects of TNF-α blockade in an animal model of depression.
abstract: Pro-inflammatory cytokines such as tumour necrosis factor-alpha (TNF-α) have repeatedly been shown to play a pivotal role in the pathophysiology of depression. Therefore, we tested the possible antidepressant-like effect of the anti-TNF-α drug etanercept in an animal model of chronic mild stress. Male Wistar rats were assigned to a non-restrained and a restrained protocol for 5 weeks. From beginning of the third week the animals were treated either with Ringer solution daily or with etanercept twice a week (0.3 mg/kg, i.p.) instead of Ringer solution (n = 12 each). As reference, imipramine (10 mg/kg, i.p.) was administered in a third restraint group daily. Naïve non-treated non-restrained rats served as healthy controls (n = 12). In the forced swim test (FST) depression-like behaviour induced by restraint was recorded as enhanced immobile time and reduced climbing activity of the vehicle-treated group in comparison to the naïve and the non-restrained vehicle treated group. The treatment with etanercept significantly reduced the depression-like effects resulting in reduced immobile time in the FST and intensified climbing behaviour (p < 0.01, p < 0.05), both similar to the antidepressive-like effect of imipramine (p < 0.01 both). The repeated restraint induced a loss of body weight gain in the Ringer-treated group which was not reversed, neither by imipramine nor by etanercept. The antidepressant effects of blocking TNF-α using etanercept may be caused by enhancement of serotonergic or noradrenergic neurotransmission or normalization of stress hormone secretion which has to be substantiated in further studies.
authors: Rudolf Boehm Institute of Pharmacology and Toxicology, Medical Faculty, University of Leipzig, Härtelstrasse 16-18, D-04107 Leipzig, Germany. ute.kruegel@medizin.uni-leipzig.de
authors: Ute
authors: U
authors: Krügel
authors: Johannes
authors: J
authors: Fischer
authors: Susanne
authors: S
authors: Radicke
authors: Ulrich
authors: U
authors: Sack
authors: Hubertus
authors: H
authors: Himmerich
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000928:Antidepressive Agents / Q000627:therapeutic use*; D001835:Body Weight / Q000187:drug effects; D003863:Depression / Q000188:drug therapy* / Q000209:etiology; D004195:Disease Models, Animal; D000068800:Etanercept; D007099:Imipramine / Q000627:therapeutic use; D007074:Immunoglobulin G / Q000627:therapeutic use*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use*; D012149:Restraint, Physical / Q000009:adverse effects; D013550:Swimming / Q000523:psychology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000928:Antidepressive Agents; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D007099:Imipramine; D000068800:Etanercept