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Neonatal Clonazepam Administration Induced Long-Lasting Changes in GABA<sub>A</sub> and GABA<sub>B</sub> Receptors
oleh: Hana Kubová, Zdeňka Bendová, Simona Moravcová, Dominika Pačesová, Luisa Rocha, Pavel Mareš
Format: | Article |
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Diterbitkan: | MDPI AG 2020-04-01 |
Deskripsi
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 GABA<sub>A</sub> receptor subunits (α1, α2, α4, γ2, and δ) and the GABA<sub>B</sub> B2 subunit, and GABA<sub>A</sub>, benzodiazepine, and GABA<sub>B</sub> 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. GABA<sub>A</sub> 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 GABA<sub>B</sub> 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.