title: Depressive-like behaviour induced by an intracerebroventricular injection of streptozotocin in mice: the protective effect of fluoxetine, antitumour necrosis factor-α and thalidomide therapies.
abstract: Information on the effect of an intracerebroventricular (i.c.v.) injection of streptozotocin (STZ) on noncognitive behaviour in rodents such as depression states is scarce. Thus, the aim of this study was to examine the depressive-like effect of STZ injected by the i.c.v. route in mice and the potential protective effect of fluoxetine, antitumour necrosis factor-α (anti-TNF-α) and thalidomide. Our results indicated that a single injection of STZ (0.1 mg/site) promoted depressive-like behaviour in the tail suspension and sucrose preference tests without altering either locomotor activity or plasma glucose levels. We also showed that STZ increased TNF-α levels in the hippocampus of mice. Fluoxetine (32 mg/kg, intraperitoneally. 30 min before STZ injection), and the anti-TNF-α antibody (0.1 pg/site, i.c.v.) and thalidomide (3 mg/kg, subcutaneously), coadministered with STZ, prevented these effects. This is the first study to report depressive-like effects of STZ using the i.c.v. route in mice. We concluded that fluoxetine, anti-TNF-α antibody and thalidomide were effective in preventing depressive-like behaviour and the increase in TNF-α levels in the hippocampus of mice induced by an i.c.v. injection of STZ, reinforcing the involvement of TNF-α in the pathophysiology of depression. This model and the mechanisms studied may contribute towards the development of new antidepressant drugs and enhance the options for studying depression.
authors: Laboratory of Pharmacological and Toxicological Reviews Applied to Bioactive Molecules - LaftamBio Pampa - Federal University of Pampa, Itaqui, RS, Brazil.
authors: Leandro C
authors: LC
authors: Souza
authors: Carlos B
authors: CB
authors: Filho
authors: Lucian D
authors: LD
authors: Fabbro
authors: Marcelo G
authors: MG
authors: de Gomes
authors: André T R
authors: AT
authors: Goes
authors: Cristiano R
authors: CR
authors: Jesse
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000008:administration & dosage / Q000627:therapeutic use; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001522:Behavior, Animal / Q000187:drug effects; D003863:Depression / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D019422:Dietary Sucrose / Q000008:administration & dosage; D004195:Disease Models, Animal; D005473:Fluoxetine / Q000627:therapeutic use*; D005518:Food Preferences / Q000187:drug effects; D019417:Hindlimb Suspension; D006624:Hippocampus / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D013311:Streptozocin; D013792:Thalidomide / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000378:metabolism
chemical_list: D057134:Antibodies, Neutralizing; D000928:Antidepressive Agents; D019422:Dietary Sucrose; D007166:Immunosuppressive Agents; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D014409:Tumor Necrosis Factor-alpha; D005473:Fluoxetine; D013792:Thalidomide; D013311:Streptozocin