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
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2016
Authors
Batinić, Bojan
Santrač, Anja

Divović, Branka

Timić, Tamara

Stanković, Tamara
Obradović, Aleksandar

Joksimović, Srđan

Savić, Miroslav

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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 Immune activation was confirmed by detecting high levels of TNF-alpha and IL-6 in dam blood withdrawn 2 h after the first dose of LPS.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.
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Behavioural Brain Research, 2016, 299, 72-80Publisher:
- Elsevier Science BV, Amsterdam
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DOI: 10.1016/j.bbr.2015.11.025
ISSN: 0166-4328
PubMed: 26620494
WoS: 000368565000010
Scopus: 2-s2.0-84949023923
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PharmacyTY - 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 . .