title: Repeated intranasal oxytocin administration in early life dysregulates the HPA axis and alters social behavior.
abstract: Agonistic interactions are a powerful stressor. Conversely, positive social interactions can reduce the adverse effects of social stress. This possibly occurs through the action of oxytocin (OT), a neuropeptide able to reduce activation of the hypothalamo-pituitary-adrenal (HPA) axis. We hypothesized that repeated OT intranasal administration to neonatal pigs could provide long-lasting protective effects against social stress. In each of six litters, two pigs per litter received 0.5 mL of saline containing 24 IU (or 50 μg) of OT intranasally and two control littermates received 0.5 mL of saline as a control at 1, 2 and 3 days of age. Contrary to our predictions, when socially mixed after weaning at 17 days of age, neonatally OT-administered pigs received more aggressive interactions and performed more aggressive interactions in return, showed greater locomotion, spent less time in social contact, and had greater cortisol concentrations than control pigs. When this social mixing was repeated at 8 weeks of age, OT pigs still performed more aggressive interactions and had greater adrenocorticotropic hormone concentrations than control pigs. A dexamethasone suppression test and corticotropic releasing hormone administration challenge at 11 weeks of age revealed that OT pigs were less responsive to dexamethasone than control pigs, suggesting a deficient HPA axis' negative feedback control. Postnatal repeated OT administration altered social behavior and resulted in a long-term dysregulation of the HPA axis. These findings highlight the complex, fine-tuning of the neurobiological mechanisms regulating the development of social behavior and suggest caution in the application of neonatal peptide treatments during early development.
authors.affiliation: Department of Animal Sciences, Purdue University, West Lafayette, IN 47907, USA. jl.rault@gmail.com
authors.forename: Jean-Loup
authors.initials: JL
authors.lastname: Rault
authors.forename: C Sue
authors.initials: CS
authors.lastname: Carter
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Garner
authors.forename: Jeremy N
authors.initials: JN
authors.lastname: Marchant
authors.forename: Brian T
authors.initials: BT
authors.lastname: Richert
authors.forename: Donald C
authors.initials: DC
authors.lastname: Lay
mesh_terms: D000281:Administration, Intranasal; D000374:Aggression / Q000187:drug effects; D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight / Q000187:drug effects; D003346:Corticotropin-Releasing Hormone / Q000008:administration & dosage; D003907:Dexamethasone; D004334:Drug Administration Schedule; D005260:Female; D006854:Hydrocortisone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010120:Oxytocics / Q000008:administration & dosage / Q000633:toxicity*; D010121:Oxytocin / Q000008:administration & dosage / Q000633:toxicity*; D010913:Pituitary-Adrenal System / Q000187:drug effects*; D012920:Social Behavior Disorders / Q000139:chemically induced*; D012930:Social Dominance; D013391:Sucking Behavior / Q000187:drug effects; D013552:Swine; D013997:Time Factors; D014886:Weaning
chemical_list: D010120:Oxytocics; D010121:Oxytocin; D003907:Dexamethasone; D003346:Corticotropin-Releasing Hormone; D006854:Hydrocortisone