title: Neonatal endotoxin exposure alters the development of social behavior and the hypothalamic-pituitary-adrenal axis in selectively bred mice.
abstract: Developmental differences in the biobehavioral consequences of immune activation in early life were investigated in two lines of mice selectively bred for high and low levels of inter-male aggressive behavior. At age 5 or 6 days, male mice were administered saline or 0.05 mg/kg gram-negative bacterial endotoxin (Escherichia coli, LPS, ip). There was a transient endotoxin-induced reduction in the growth rate of the neonates in the high-aggressive line. At age 45-50 days, the animals' behaviors were assessed in a dyadic task. Hypothalami and sera were harvested 20 min later. Rates of socially reactive behaviors to conspecific contact (i.e., kick, startle) were increased in the endotoxin-treated groups from both lines. For the high-aggressive line only, endotoxin treatment increased behavioral immobility, decreased attack frequency, and decreased levels of hypothalamic corticotrophin-releasing factor (CRF). The effects of endotoxin exposure in early life on socially reactive behaviors in later life were associated with endotoxin-induced individual differences in CRF levels in the high-aggressive line but not the low-aggressive line. The findings demonstrate long-term social developmental consequences of immune activation during the neonatal period.
authors.affiliation: Department of Biobehavioral Health, Pennsylvania State University, University Park 16802, USA. DAG11@PSUVM.PSU.EDU
authors.forename: D A
authors.initials: DA
authors.lastname: Granger
authors.forename: K E
authors.initials: KE
authors.lastname: Hood
authors.forename: S C
authors.initials: SC
authors.lastname: Ikeda
authors.forename: C L
authors.initials: CL
authors.lastname: Reed
authors.forename: M L
authors.initials: ML
authors.lastname: Block
mesh_terms: D000374:Aggression / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology* / Q000523:psychology*; D003345:Corticosterone / Q000097:blood; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism; D004731:Endotoxins / Q000633:toxicity*; D004926:Escherichia coli / Q000378:metabolism; D006128:Growth / Q000187:drug effects; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000254:growth & development* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000254:growth & development*; D011863:Radioimmunoassay; D012919:Social Behavior; D012934:Social Isolation
chemical_list: D004731:Endotoxins; D008070:Lipopolysaccharides; C044101:endotoxin, Escherichia coli; D003346:Corticotropin-Releasing Hormone; D003345:Corticosterone