Does Chronic Administration of Sodium Valproate to Juvenile Rats Induce Movement Disorder and Cognitive Dysfunction during Adulthood?
Background: Children with seizure disorder are often treated with sodium valproate (SV) on long-term basis. SV acts mainly through gamma amino butyric acid pathways, reducing the excitatory neurotransmission and modifying the monoamine concentration. Altered monoamine concentration by SV is expected...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Arak University of Medical Sciences
2018-01-01
|
| Series: | Iranian Journal of Toxicology |
| Subjects: | |
| Online Access: | https://ijt.arakmu.ac.ir/article-1-626-en.pdf |
| _version_ | 1811281510173507584 |
|---|---|
| author | Namitha Nair Sampath Madhyastha Priyanka Chitti Teresa Joy Vandana Blossom |
| author_facet | Namitha Nair Sampath Madhyastha Priyanka Chitti Teresa Joy Vandana Blossom |
| author_sort | Namitha Nair |
| collection | DOAJ |
| description | Background: Children with seizure disorder are often treated with sodium valproate (SV) on long-term basis. SV acts mainly through gamma amino butyric acid pathways, reducing the excitatory neurotransmission and modifying the monoamine concentration. Altered monoamine concentration by SV is expected to cause movement disorder and cognitive dysfunction, considered reversible after the withdrawal of treatment, but some claim it to be irreversible. It is not clear whether such adverse effects continue during adulthood. The aim of this study was to investigate whether chronic administration of SV in juvenile rats causes movement disorder and cognitive dysfunction during their early adulthood.
Methods: Sixteen-day-old male Wistar rats from the central animal house, KMC, Mangalore, India in 2015, received either 200 or 400 mg/kg dose of SV for 45 consecutive days and another group served as control. Thirty days after discontinuation of the drug, at postnatal day 90, the rats were tested for movement disorder and cognitive function.
Results: Chronic SV treatment in juvenile rats resulted in slow movement, tremors during adulthood but did not affect muscle tone, locomotor and exploratory activities. It also caused cognitive dysfunction in adult rats.
Conclusion: Despite the reported safety of chronic SV therapy, its adverse effects such as Parkinsonism symptoms or cognitive dysfunctions should be of concern in all young patients treated with SV for many years. Persistence of cognitive impairment, tremors and generalized slow movement during adulthood after cessation of treatment that was observed in this study, warrants a close monitoring system in children who receive long-term sodium valproate. |
| first_indexed | 2024-04-13T01:34:57Z |
| format | Article |
| id | doaj.art-10c22e70363c4423aa6cff9511579bfc |
| institution | Directory Open Access Journal |
| issn | 2008-2967 2251-9459 |
| language | English |
| last_indexed | 2024-04-13T01:34:57Z |
| publishDate | 2018-01-01 |
| publisher | Arak University of Medical Sciences |
| record_format | Article |
| series | Iranian Journal of Toxicology |
| spelling | doaj.art-10c22e70363c4423aa6cff9511579bfc2022-12-22T03:08:23ZengArak University of Medical SciencesIranian Journal of Toxicology2008-29672251-94592018-01-011213946Does Chronic Administration of Sodium Valproate to Juvenile Rats Induce Movement Disorder and Cognitive Dysfunction during Adulthood?Namitha Nair 0 Sampath Madhyastha1Priyanka Chitti 2Teresa Joy 3Vandana Blossom 4Department of Anatomy, Kasturba Medical College, Manipal University, Mangalore, India.Department of Anatomy, Faculty of Medicine, Kuwait University, Jabriya, Kuwait. * Corresponding Author: E-mail: madhyast@yahoo.comDepartment of Anatomy, Kasturba Medical College, Manipal University, Mangalore, India.Department of Anatomy, Kasturba Medical College, Manipal University, Mangalore, India.Department of Anatomy, Kasturba Medical College, Manipal University, Mangalore, India.Background: Children with seizure disorder are often treated with sodium valproate (SV) on long-term basis. SV acts mainly through gamma amino butyric acid pathways, reducing the excitatory neurotransmission and modifying the monoamine concentration. Altered monoamine concentration by SV is expected to cause movement disorder and cognitive dysfunction, considered reversible after the withdrawal of treatment, but some claim it to be irreversible. It is not clear whether such adverse effects continue during adulthood. The aim of this study was to investigate whether chronic administration of SV in juvenile rats causes movement disorder and cognitive dysfunction during their early adulthood. Methods: Sixteen-day-old male Wistar rats from the central animal house, KMC, Mangalore, India in 2015, received either 200 or 400 mg/kg dose of SV for 45 consecutive days and another group served as control. Thirty days after discontinuation of the drug, at postnatal day 90, the rats were tested for movement disorder and cognitive function. Results: Chronic SV treatment in juvenile rats resulted in slow movement, tremors during adulthood but did not affect muscle tone, locomotor and exploratory activities. It also caused cognitive dysfunction in adult rats. Conclusion: Despite the reported safety of chronic SV therapy, its adverse effects such as Parkinsonism symptoms or cognitive dysfunctions should be of concern in all young patients treated with SV for many years. Persistence of cognitive impairment, tremors and generalized slow movement during adulthood after cessation of treatment that was observed in this study, warrants a close monitoring system in children who receive long-term sodium valproate.https://ijt.arakmu.ac.ir/article-1-626-en.pdfChoreaCognitive ManifestationMovement DisordersParkinsonian DisordersRatsValproic Acid |
| spellingShingle | Namitha Nair Sampath Madhyastha Priyanka Chitti Teresa Joy Vandana Blossom Does Chronic Administration of Sodium Valproate to Juvenile Rats Induce Movement Disorder and Cognitive Dysfunction during Adulthood? Iranian Journal of Toxicology Chorea Cognitive Manifestation Movement Disorders Parkinsonian Disorders Rats Valproic Acid |
| title | Does Chronic Administration of Sodium Valproate to Juvenile Rats Induce Movement Disorder and Cognitive Dysfunction during Adulthood? |
| title_full | Does Chronic Administration of Sodium Valproate to Juvenile Rats Induce Movement Disorder and Cognitive Dysfunction during Adulthood? |
| title_fullStr | Does Chronic Administration of Sodium Valproate to Juvenile Rats Induce Movement Disorder and Cognitive Dysfunction during Adulthood? |
| title_full_unstemmed | Does Chronic Administration of Sodium Valproate to Juvenile Rats Induce Movement Disorder and Cognitive Dysfunction during Adulthood? |
| title_short | Does Chronic Administration of Sodium Valproate to Juvenile Rats Induce Movement Disorder and Cognitive Dysfunction during Adulthood? |
| title_sort | does chronic administration of sodium valproate to juvenile rats induce movement disorder and cognitive dysfunction during adulthood |
| topic | Chorea Cognitive Manifestation Movement Disorders Parkinsonian Disorders Rats Valproic Acid |
| url | https://ijt.arakmu.ac.ir/article-1-626-en.pdf |
| work_keys_str_mv | AT namithanair doeschronicadministrationofsodiumvalproatetojuvenileratsinducemovementdisorderandcognitivedysfunctionduringadulthood AT sampathmadhyastha doeschronicadministrationofsodiumvalproatetojuvenileratsinducemovementdisorderandcognitivedysfunctionduringadulthood AT priyankachitti doeschronicadministrationofsodiumvalproatetojuvenileratsinducemovementdisorderandcognitivedysfunctionduringadulthood AT teresajoy doeschronicadministrationofsodiumvalproatetojuvenileratsinducemovementdisorderandcognitivedysfunctionduringadulthood AT vandanablossom doeschronicadministrationofsodiumvalproatetojuvenileratsinducemovementdisorderandcognitivedysfunctionduringadulthood |