Insulin-like growth factor-I peptides act centrally to decrease depression-like behavior of mice treated intraperitoneally with lipopolysaccharide

Centrally administered insulin-like growth factor (igf)-i has anti-depressant activity in several rodent models,including lipopolysaccharide (lps)-induced depression. in this study we tested the ability of igf-i and gpe (the n-terminal tri-peptide derived from igf-i) to alter depression-like behavior induced by intraperitoneal (i.p.) administration of lps in a preventive and curative manner. in the first case,igf-i (1 μg) or gpe (5 μg) was administered i.c.v. to cd-1 mice followed 30 min later by 330 μg/kg body weight i.p. lps. in the second case,830 μg/kg body weight lps was given 24 h prior to either igf-i or gpe. when administered i.p.,lps induced full-blown sickness assessed as a loss of body weight,decrease in food intake and sickness behavior. none of these indices were affected by igf-i or gpe. lps also induced depression-like behavior; assessed as an increased duration of immobility in the tail suspension and forced swim tests. when administered before or after lps,igf-i and gpe abrogated the lps response; attenuating induction of depression-like behaviors and blocking preexistent depression-like behaviors. similar to previous work with igf-i,gpe decreased brain expression of cytokines in response to lps although unlike igf-i,gpe did not induce the expression of brain-derived neurotrophic factor (bdnf). lps induced expression of tryptophan dioxygenases,ido1,ido2 and tdo2,but expression of these enzymes was not altered by gpe. thus,both igf-i and gpe elicit specific improvement in depression-like behavior independent of sickness,an action that could be due to their anti-inflammatory properties. © 2011 park et al; licensee biomed central ltd.