title: A new animal model of (chronic) depression induced by repeated and intermittent lipopolysaccharide administration for 4 months.
abstract: Chronic activation of immune-inflammatory and oxidative and nitrosative stress (O&NS) pathways plays an important role in the pathophysiology of clinical depression. Increased IgA responses directed against LPS of gram-negative bacteria, indicating increased bacterial translocation, may be one of the drivers underpinning these pathways. There is a strong association between signs of bacterial translocation and chronicity of depression and O&NS, but not pro-inflammatory cytokines. The aims of the present study were to: (1) develop a new neurobehavioral model of (chronic) depression (anhedonic behavior) that may reflect chronic LPS stimulation and is associated with increased oxidative stress, and (2) to delineate the effects of fluoxetine on this new depression model. We established that in female mice repeated LPS injections once daily for 5 days (from 750 μg/kg to a maximal dose 1250 μg/kg; increasing doses for the first three days which were then gradually decreased on day 4 and 5) at a one-month interval and this repeated for 4 consecutive months induced chronic anhedonia (estimated by the preference to drink a 1% sucrose) lasting for at least 7 weeks. Chronic LPS administration significantly decreased thymus weight, proliferative activity of splenocytes, production of interferon (IFN)γ and interleukin-(IL)10, and increased superoxide and corticosterone production. Treatment with fluoxetine for 3 weeks abolished the neurobehavioral effects of LPS. The antidepressant effect of fluoxetine was accompanied by increased production of IL-10 and reduced superoxide and corticosterone production. Our results suggest that repeated intermittent LPS injections to female mice may be a useful model of chronic depression and in particular for the depressogenic effects of long standing activation of the toll-like receptor IV complex.
authors: Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Science, 31-343 Krakow, Poland. kubera@if-pan.krakow.pl
authors: Marta
authors: M
authors: Kubera
authors: Katarzyna
authors: K
authors: Curzytek
authors: Weronika
authors: W
authors: Duda
authors: Monika
authors: M
authors: Leskiewicz
authors: Agnieszka
authors: A
authors: Basta-Kaim
authors: Boguslawa
authors: B
authors: Budziszewska
authors: Adam
authors: A
authors: Roman
authors: Alena
authors: A
authors: Zajicova
authors: Vladimir
authors: V
authors: Holan
authors: Ewa
authors: E
authors: Szczesny
authors: Wladyslaw
authors: W
authors: Lason
authors: Michael
authors: M
authors: Maes
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D002755:Choice Behavior / Q000187:drug effects; D003863:Depression / Q000139:chemically induced* / Q000503:physiopathology; D003866:Depressive Disorder / Q000139:chemically induced* / Q000503:physiopathology; D004195:Disease Models, Animal; D004435:Eating / Q000187:drug effects; D005260:Female; D005473:Fluoxetine / Q000494:pharmacology*; D008070:Lipopolysaccharides; D051379:Mice; D013395:Sucrose / Q000494:pharmacology; D013950:Thymus Gland / Q000187:drug effects
chemical_list: D000928:Antidepressive Agents; D008070:Lipopolysaccharides; D005473:Fluoxetine; D013395:Sucrose