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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

Authorized Users Only
2016
Authors
Batinić, Bojan
Santrač, Anja
Divović, Branka
Timić, Tamara
Stanković, Tamara
Obradović, Aleksandar
Joksimović, Srđan
Savić, Miroslav
Article (Published version)
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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 mu g/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 Immune activation was confirmed by detecting high levels of TNF-alpha and IL-6 in dam blood withdrawn 2 h after the first dose of LPS.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 0.5 mg/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.

Source:
Behavioural Brain Research, 2016, 299, 72-80
Publisher:
  • Elsevier Science BV, Amsterdam
Funding / projects:
  • Behavioral ?ffects following repeated administration of newly synthesized ligands selective for distinct subtypes of GABAA receptor benzodiazepine binding site: comparison with standard psychopharmacologic drugs (RS-175076)

DOI: 10.1016/j.bbr.2015.11.025

ISSN: 0166-4328

PubMed: 26620494

WoS: 000368565000010

Scopus: 2-s2.0-84949023923
[ Google Scholar ]
32
23
URI
https://farfar.pharmacy.bg.ac.rs/handle/123456789/2558
Collections
  • Radovi istraživača / Researchers’ publications
Institution/Community
Pharmacy
TY  - JOUR
AU  - Batinić, Bojan
AU  - Santrač, Anja
AU  - Divović, Branka
AU  - Timić, Tamara
AU  - Stanković, Tamara
AU  - Obradović, Aleksandar
AU  - Joksimović, Srđan
AU  - Savić, Miroslav
PY  - 2016
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2558
AB  - 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 mu g/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-alpha and IL-6 in dam blood withdrawn 2 h 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 0.5 mg/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.
PB  - Elsevier Science BV, Amsterdam
T2  - Behavioural Brain Research
T1  - 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
VL  - 299
SP  - 72
EP  - 80
DO  - 10.1016/j.bbr.2015.11.025
ER  - 
@article{
author = "Batinić, Bojan and Santrač, Anja and Divović, Branka and Timić, Tamara and Stanković, Tamara and Obradović, Aleksandar and Joksimović, Srđan and Savić, Miroslav",
year = "2016",
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 mu g/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-alpha and IL-6 in dam blood withdrawn 2 h 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 0.5 mg/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.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "Behavioural Brain Research",
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",
volume = "299",
pages = "72-80",
doi = "10.1016/j.bbr.2015.11.025"
}
Batinić, B., Santrač, A., Divović, B., Timić, T., Stanković, T., Obradović, A., Joksimović, S.,& Savić, M.. (2016). 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. in Behavioural Brain Research
Elsevier Science BV, Amsterdam., 299, 72-80.
https://doi.org/10.1016/j.bbr.2015.11.025
Batinić B, Santrač A, Divović B, Timić T, Stanković T, Obradović A, Joksimović S, Savić M. 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. in Behavioural Brain Research. 2016;299:72-80.
doi:10.1016/j.bbr.2015.11.025 .
Batinić, Bojan, Santrač, Anja, Divović, Branka, Timić, Tamara, Stanković, Tamara, Obradović, Aleksandar, Joksimović, Srđan, Savić, Miroslav, "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" in Behavioural Brain Research, 299 (2016):72-80,
https://doi.org/10.1016/j.bbr.2015.11.025 . .

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