title: Neonatal proinflammatory challenge in male Wistar rats: Effects on behavior, synaptic plasticity, and adrenocortical stress response.
abstract: Effects of neonatal proinflammatory stress (NPS) on the development of anxiety and depressive-like behavior, stress responsiveness, hippocampal plasticity and conditioned fear response were studied in adolescent and adult male Wistar rats. On PND 3 and PND 5, the pups were subcutaneously injected with bacterial lipopolysaccharide (LPS, 50 μg/kg). In the open field test, signs of increased anxiety were demonstrated in adolescent (PND 32), but not in adult (PND 101) rats. In the elevated plus maze, no changes could be detected in adolescent rats, however, in the adults the number of entries into the open arms decreased suggesting increased anxiety after NPS. Signs of "behavioral despair" in the forced swim test, expressed in adolescent rats as a trend, became significant in the adults indicating depression-like behavior. In the majority of brain slices from PND 19-PND 33 rats subjected to NPS, deficit of LTP in the hippocampal CA1 field was detected, this deficit being associated with the impaired mechanisms of LTP induction. In the adult rats, NPS enhanced fear conditioning promoting improved formation of the novel context-foot shock association in the contextual fear conditioning paradigm without effect on cued fear conditioning. NPS significantly impaired functioning of the hypothalamic-pituitary-adrenal axis (HPAA), resulting in an elevated corticosterone level maintained in the adolescents but not in the adults and in modified corticosterone response to behavioral sub-chronic stress in both adolescent and adult rats. Thus, NPS induces "perinatal malprogramming" resulting in development of depression-like behaviors, associated with abnormalities in functioning of the HPAA, impaired hippocampal neuroplasticity (LTP) and changes in hippocampus-dependent memory formation.
authors: Department of Functional Biochemistry of the Nervous System, Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, Moscow 117485, Russia.
authors: Anna
authors: A
authors: Tishkina
authors: Department of Functional Biochemistry of the Nervous System, Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, Moscow 117485, Russia.
authors: Mikhail
authors: M
authors: Stepanichev
authors: Department of Functional Biochemistry of the Nervous System, Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, Moscow 117485, Russia.
authors: Irina
authors: I
authors: Kudryashova
authors: Department of Functional Biochemistry of the Nervous System, Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, Moscow 117485, Russia.
authors: Sofia
authors: S
authors: Freiman
authors: Department of Functional Biochemistry of the Nervous System, Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, Moscow 117485, Russia.
authors: Mikhail
authors: M
authors: Onufriev
authors: Department of Functional Biochemistry of the Nervous System, Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, Moscow 117485, Russia.
authors: Natalia
authors: N
authors: Lazareva
authors: Department of Functional Biochemistry of the Nervous System, Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, Moscow 117485, Russia. Electronic address: nata_gul@yahoo.com.
authors: Natalia
authors: N
authors: Gulyaeva
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001007:Anxiety / Q000139:chemically induced / Q000503:physiopathology*; D003213:Conditioning, Psychological / Q000187:drug effects; D003345:Corticosterone / Q000097:blood*; D003863:Depression / Q000139:chemically induced / Q000503:physiopathology*; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology*; D005239:Fear / Q000187:drug effects / Q000502:physiology*; D005260:Female; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D013550:Swimming / Q000523:psychology
chemical_list: D008070:Lipopolysaccharides; D003345:Corticosterone
keywords: Anxiety; Contextual fear conditioning; Corticosterone; Depression; Hippocampus; Hypothalamic–pituitary–gonadal axis; Lipopolysaccharide; Long term potentiation; Maturation; Neonatal proinflammatory stress