The effect of early handling on anxiety-like behaviors of rats exposed to valproic acid pre-and post-natally.

Autor: Shafaghi A; Department of Pharmaceutical Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran., Vakili Shahrbabaki SS; Department of Biology, University of Turku, Turku, Finland; Physiology Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran., Aminzadeh A; Department of Toxicology and Pharmacology, Faculty of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran. Electronic address: a.aminzadeh@kmu.ac.ir., Heidari MR; Department of Toxicology and Pharmacology, Faculty of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran; Pharmaceutical Research Center, Kerman University of Medical Sciences, Kerman, Iran. Electronic address: heidarimr@kmu.ac.ir., Shamsi Meymandi M; Pathology and Stem Cells Research Center, Kerman Medical School, Kerman University of Medical Sciences, Kerman, Iran.; Neuroscience Research Center, Institute of Neuropharmacology, Department of Physiology and Pharmacology, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran.. Electronic address: manzume@yahoo.com., Bashiri H; Neuroscience Research Center, Institute of Neuropharmacology, Department of Physiology and Pharmacology, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran.; Sirjan Faculty of Medical Science, Sirjan, Iran.. Electronic address: h.bashiri@kmu.ac.ir.
Jazyk: angličtina
Zdroj: Neurotoxicology and teratology [Neurotoxicol Teratol] 2022 Jan-Feb; Vol. 89, pp. 107050. Date of Electronic Publication: 2021 Nov 18.
DOI: 10.1016/j.ntt.2021.107050
Abstrakt: Introduction: Autism spectrum disorder (ASD) is a complex, behaviorally defined disorder of the immature brain as a result of genetic and environmental risk factors, such as prenatal exposure to valproic acid (VPA). This syndrome is known for its high prevalence. On the other hand, postnatal manipulations have been shown to affect brain development, cortical neuroscience, and pituitary-adrenal activity. In early handling (EH) procedure, pups are removed from their mother on a daily basis from birth to lactation, are physically touched, and exposed to the (a) new environment. In the present study, the effect of EH on anxiety-like behaviors in rats exposed pre- and post-natally to valproic acid was investigated.
Methods: Pregnant Wistar rats were randomly separated into six groups which are prenatal saline, Prenatal VPA, Prenatal VPA + EH and postnatal saline, Postnatal VPA, Postnatal VPA + EH. VPA administration was performed either on ED12.5 (600 mg/kg, i.p.) or PD 2-4 (400 mg/kg, s.c.). In the groups receiving EH, pups underwent physical handling from PD 1 to 21. On postnatal day 21 all offspring were weaned and the behavioral tests were performed on 30 and 31 days of age. Elevated plus maze and open field tests were used to investigate anxiety-like behaviors.
Results: The results revealed that intraperitoneal injection of valrpoic acid (600 mg.kg) during pregnancy significantly reduced OAT% in males (p < 0.01) and females in a non-significant manner (p > 0.05). In comparison, rearing counts of prenatal VPA groups significantly increased in female sex (p < 0.05) in the EPM test. Following postnatal VPA administration (400 mg/kg), decrease in the time spent in central zone occurred in female rats in the open filed (p < 0.05), as well as a significant increase in the number of grooming of the male sex (p < 0.05). Applying Early Handling to male and female Wistar rats receiving prenatal VPA significantly reversed the OAT% fall (p < 0.05). EH in postnatally VPA exposed animals significantly decreased the OAT% and OAE% criteria, while increasing the locomotor activity of the female sex (p < 0.05). Compared with the postnatal VPA group, no significant change was reported in the EPM performance of postnatal VPA + EH group in neither of sexes (p > 0.05).
Conclusion: The findings of this study suggest that injections of valproic acid during pregnancy lead to anxiety-like behaviors in male offspring, which EH can improve (attenuate) to some extent. VPA injections on the second to the fourth day of infancy did not have a profound effect on anxiety level. Further behavioral studies need to be performed using other devices to investigate anxiety-like behaviors and to determine the mechanisms involved in these behaviors.
(Copyright © 2021. Published by Elsevier Inc.)
Databáze: MEDLINE
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