title: Early deprivation leads to altered behavioural, autonomic and endocrine responses to environmental challenge in adult Fischer rats.
abstract: Depression is diagnosed on the basis of abnormal positive affects (anhedonia) and negative affects (low mood, helplessness, coping deficit, fatigue), and associated physiological abnormalities include hyperactivity of the HPA endocrine system and autonomic nervous system. Adverse early life environments, including parent-offspring emotional and physical neglect, are associated with traits of altered physiological and neurobiological function and long-term predisposition to depression. Animal studies based on early life adversity can potentially yield environmental models of the developmental behavioural neurobiology of depression. In Wistar rats, we demonstrated that isolation of pups from dam and littermates at room temperature for 4 h per day on P1-14 (early deprivation, ED) led to adulthood anhedonia-like traits of reduced motivation to obtain gustatory reward and reduced social motivation, relative to subjects left undisturbed during infancy (non-handling, NH). We hypothesized that the depression-like effects of ED would be even more pronounced and multiple in the stress hyper-responsive Fischer rat strain. The effects of ED were studied relative to NH and 15 min of daily isolation (early handling, EH). Relative to NH and EH, which exhibited remarkably similar phenotypes, ED led, principally in males, to chronic traits of: reduced motivation for and consumption of gustatory reward; increased activity in the pre-test and test phases of the forced swim test; reduced coping behaviour in an aversive environment; attenuated plasma corticosterone stress response to a normal plasma ACTH stress response; increased hypertensive response to a novel environment; and increased prefrontal cortical serotonin. High sensitivity to an aversive early environment in male Fischer rats therefore constitutes an important model for the study of affective development and its neurobiology.
authors.affiliation: Behavioural Neurobiology Laboratory, Swiss Federal Institute of Technology Zurich, Schorenstrasse 16, CH-8603 Schwerzenbach, Switzerland.
authors.forename: Daniela
authors.initials: D
authors.lastname: Rüedi-Bettschen
authors.forename: Weining
authors.initials: W
authors.lastname: Zhang
authors.forename: Holger
authors.initials: H
authors.lastname: Russig
authors.forename: Boris
authors.initials: B
authors.lastname: Ferger
authors.forename: Anna
authors.initials: A
authors.lastname: Weston
authors.forename: Else-Marie
authors.initials: EM
authors.lastname: Pedersen
authors.forename: Joram
authors.initials: J
authors.lastname: Feldon
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Pryce
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001341:Autonomic Nervous System / Q000502:physiology*; D001362:Avoidance Learning / Q000502:physiology; D001522:Behavior, Animal / Q000502:physiology*; D015306:Biogenic Monoamines / Q000378:metabolism; D001923:Brain Chemistry / Q000502:physiology; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003345:Corticosterone / Q000097:blood; D004703:Endocrine System / Q000502:physiology*; D004777:Environment; D004924:Escape Reaction / Q000502:physiology; D005260:Female; D008297:Male; D008425:Maternal Behavior / Q000502:physiology; D008426:Maternal Deprivation; D011863:Radioimmunoassay / Q000379:methods; D051381:Rats; D011916:Rats, Inbred F344; D012055:Reinforcement Schedule; D012054:Reinforcement, Psychology; D012149:Restraint, Physical / Q000379:methods; D012737:Sex Factors
chemical_list: D015306:Biogenic Monoamines; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone