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Neonatal Clonazepam Administration Induced Long-Lasting Changes in GABAA and GABAB Receptors
H. Kubová, Z. Bendová, S. Moravcová, D. Pačesová, L. Rocha, P. Mareš
Jazyk angličtina Země Švýcarsko
Typ dokumentu časopisecké články
Grantová podpora
CZ.CZ.02.1.01/0.0/0.0/16_025/0007444
European Regional Development Fund
19-11931S
Grantová Agentura České Republiky
67985823
support for long-term conceptual development of research organization RVO
SVV-260434/2019
Institutional Project of the Ministry of Education, Youth and Sport of the Czech Republic
Free Medical Journals od 2000
Freely Accessible Science Journals od 2000
PubMed Central od 2007
Europe PubMed Central od 2007
ProQuest Central od 2000-03-01
Open Access Digital Library od 2000-01-01
Open Access Digital Library od 2007-01-01
Health & Medicine (ProQuest) od 2000-03-01
ROAD: Directory of Open Access Scholarly Resources od 2000
Odkazy
PubMed
32366006
DOI
10.3390/ijms21093184
Knihovny.cz E-zdroje
- MeSH
- benzodiazepiny farmakologie MeSH
- GABA metabolismus MeSH
- hipokampus účinky léků metabolismus MeSH
- klonazepam farmakologie MeSH
- krysa rodu rattus MeSH
- kvantitativní polymerázová řetězová reakce MeSH
- mozek účinky léků metabolismus MeSH
- novorozená zvířata MeSH
- potkani inbrední WF MeSH
- receptory GABA-A metabolismus MeSH
- receptory GABA-B metabolismus MeSH
- vazba proteinů MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Benzodiazepines (BZDs) are widely used in patients of all ages. Unlike adults, neonatal animals treated with BZDs exhibit a variety of behavioral deficits later in life; however, the mechanisms underlying these deficits are poorly understood. This study aims to examine whether administration of clonazepam (CZP; 1 mg/kg/day) in 7-11-day-old rats affects Gama aminobutyric acid (GABA)ergic receptors in both the short and long terms. Using RT-PCR and quantitative autoradiography, we examined the expression of the selected GABAA receptor subunits (α1, α2, α4, γ2, and δ) and the GABAB B2 subunit, and GABAA, benzodiazepine, and GABAB receptor binding 48 h, 1 week, and 2 months after treatment discontinuation. Within one week after CZP cessation, the expression of the α2 subunit was upregulated, whereas that of the δ subunit was downregulated in both the hippocampus and cortex. In the hippocampus, the α4 subunit was downregulated after the 2-month interval. Changes in receptor binding were highly dependent on the receptor type, the interval after treatment cessation, and the brain structure. GABAA receptor binding was increased in almost all of the brain structures after the 48-h interval. BZD-binding was decreased in many brain structures involved in the neuronal networks associated with emotional behavior, anxiety, and cognitive functions after the 2-month interval. Binding of the GABAB receptors changed depending on the interval and brain structure. Overall, the described changes may affect both synaptic development and functioning and may potentially cause behavioral impairment.
Faculty of Science Charles University 12800 Prague Czech Republic
Institute of Physiology Academy of Sciences of the Czech Republic 14220 Prague Czech Republic
National Institute of Mental Health 25067 Klecany Czech Republic
Pharmacobiology Department Center of Research and Advanced Studies Mexico City 14330 Mexico
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