title: Moderate neonatal stress decreases within-group variation in behavioral, immune and HPA responses in adult mice.
abstract: BACKGROUND
  The significance of behavioral neuroscience and the validity of its animal models of human pathology largely depend on the possibility to replicate a given finding across different laboratories. Under the present test and housing conditions, this axiom fails to resist the challenge of experimental validation. When several mouse strains are tested on highly standardized behavioral test batteries in different laboratories, significant strain x lab interactions are often detected. This limitation, predominantly due to elevated within-group variability observed in control subjects, increases the number of animals needed to address fine experimental questions. Laboratory rodents display abnormal stress and fear reactions to experimental testing, which might depend on the discrepancy between the stability of the neonatal environment and the challenging nature of the adult test and housing conditions.
  
  
  RESULTS
  Stimulating neonatal environments (e.g. brief maternal separations, increased foraging demands or maternal corticosterone supplementation) reduce stress and fear responses in adulthood. Here we tested whether reduced fearfulness associated with experimental testing would also reduce inter-individual variation. In line with our predictions, we show that a moderate elevation in neonatal corticosterone through maternal milk significantly reduces fear responses and inter-individual variability (average 44%) in adult mouse offspring.
  
  
  CONCLUSIONS
  We observed reduced variation in pain perception, novelty preference, hormonal stress response and resistance to pathogen infection. This suggests that the results of this study may apply to a relatively broad spectrum of neuro-behavioral domains. Present findings encourage a reconsideration of the basic principles of neonatal housing systems to improve the validity of experimental models and reduce the number of animals used.
authors.affiliation: Section of Behavioural Neuroscience, Department of Cell Biology and Neuroscience, Istituto Superiore di Sanità, Roma, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Macrì
authors.forename: Paolo
authors.initials: P
authors.lastname: Pasquali
authors.forename: Luca Tommaso
authors.initials: LT
authors.lastname: Bonsignore
authors.forename: Stefano
authors.initials: S
authors.lastname: Pieretti
authors.forename: Francesca
authors.initials: F
authors.lastname: Cirulli
authors.forename: Flavia
authors.initials: F
authors.lastname: Chiarotti
authors.forename: Giovanni
authors.initials: G
authors.lastname: Laviola
mesh_terms: D000305:Adrenal Cortex Hormones / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn / Q000276:immunology*; D001522:Behavior, Animal; D005260:Female; D014644:Genetic Variation; D007030:Hypothalamo-Hypophyseal System; D007107:Immune System; D008297:Male; D051379:Mice; D010146:Pain; D010913:Pituitary-Adrenal System; D011247:Pregnancy; D012107:Research Design; D013045:Species Specificity
chemical_list: D000305:Adrenal Cortex Hormones