title: Lipopolysaccharide exposure during late embryogenesis results in diminished locomotor activity and amphetamine response in females and spatial cognition impairment in males in adult, but not adolescent rat offspring.
abstract: Numerous basic and epidemiological studies have connected prenatal maternal immune activation with the occurrence of schizophrenia and/or autism. Depending on subtle differences in protocols of the used animal model, a variety of behavioral abnormalities has been reported. This study investigated behavioral differences in Wistar rat offspring of both genders, exposed to the 100 μg/kg per day dose of lipopolysaccharide (LPS) in late embryogenesis (embryonic days 15 and 16), while tested at their adolescent and young adult age (postnatal days 40 and 60, respectively). Immune activation was confirmed by detecting high levels of TNF-α and IL-6 in dam blood withdrawn 2h after the first dose of LPS. The animals were assessed in three consecutive trials of locomotor activity (novelty exploration, response to i.p. saline injection and challenge with 0.5mg/kg amphetamine), Morris water maze and social interaction tests. Overt behavioral dysfunction was perceived in adult rats only, and these changes were gender-distinctive. When compared with control rats, LPS females displayed baseline hypolocomotion and a decreased reactivity to amphetamine, while LPS males exhibited spatial learning (acquisition trials) and memory (probe trial) impairments. Prenatal treatment did not affect the time spent in social interaction. As maternal exposure to LPS in late gestation resulted in behavioral changes in offspring in early adulthood, it may model schizophrenia-like, but not autism-like endophenotypes. However, lack of a potentiated response to amphetamine testified that this model could not mimic positive symptoms, but rather certain traits of cognitive dysfunction and deficit symptoms, in males and females, respectively.
authors.affiliation: Department of Physiology, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, 11221 Belgrade, Serbia.
authors.forename: Bojan
authors.initials: B
authors.lastname: Batinić
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, 11221 Belgrade, Serbia.
authors.forename: Anja
authors.initials: A
authors.lastname: Santrač
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, 11221 Belgrade, Serbia.
authors.forename: Branka
authors.initials: B
authors.lastname: Divović
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, 11221 Belgrade, Serbia.
authors.forename: Tamara
authors.initials: T
authors.lastname: Timić
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, 11221 Belgrade, Serbia.
authors.forename: Tamara
authors.initials: T
authors.lastname: Stanković
authors.affiliation: Department of Physiology, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, 11221 Belgrade, Serbia.
authors.forename: Aleksandar Lj
authors.initials: ALj
authors.lastname: Obradović
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, 11221 Belgrade, Serbia.
authors.forename: Srđan
authors.initials: S
authors.lastname: Joksimović
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, University of Belgrade, Vojvode Stepe 450, 11221 Belgrade, Serbia. Electronic address: miroslav@pharmacy.bg.ac.rs.
authors.forename: Miroslav M
authors.initials: MM
authors.lastname: Savić
mesh_terms: D000661:Amphetamine / Q000008:administration & dosage; D000818:Animals; D001321:Autistic Disorder / Q000209:etiology; D001522:Behavior, Animal; D003071:Cognition / Q000187:drug effects*; D004195:Disease Models, Animal; D005260:Female; D015850:Interleukin-6 / Q000097:blood / Q000276:immunology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D018811:Maternal Exposure; D009043:Motor Activity / Q000276:immunology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar; D012559:Schizophrenia / Q000209:etiology; D012737:Sex Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D000661:Amphetamine
keywords: Autism; Gender differences; Maternal immune activation; Morris water maze; Schizophrenia; Social interaction