TY  - JOUR
AU  - Martinović, Jelena
AU  - Samardžić, Janko
AU  - Zarić Kontić, Marina
AU  - Ivković, Sanja
AU  - Dacić, Sanja
AU  - Major, Tamara
AU  - Radosavljević, Milica
AU  - Svob Strac, Dubravka
PY  - 2023
UR  - https://vinar.vin.bg.ac.rs/handle/123456789/12975
AB  - Zaleplon is a positive allosteric modulator of the γ-aminobutyric acid (GABA)A receptor approved for the short-term treatment of insomnia. Previous publications on zaleplon have not addressed the proteins involved in its mechanism of action but have mostly referred to behavioral or pharmacological studies. Since both GABAergic and glutamatergic signaling have been shown to regulate wakefulness and sleep, we examined the effects of prolonged zaleplon treatment (0.625 mg/kg for 5 days) on these systems in the hippocampus of male Wistar rats. Western blot and immunohistochemical analyses showed that the upregulated components of GABAergic signaling (glutamate decarboxylase, vesicular GABA transporter, GABA, and α1 subunit of the GABAA receptor) were accompanied by increased protein levels in the glutamatergic system (vesicular glutamate transporter 1 and NR1, NR2A, and NR2B subunits of N-methyl-d-aspartate receptor). Our results, showing that zaleplon enhances GABA neurotransmission in the hippocampus, were not surprising. However, we found that treatment also increased glutamatergic signaling. This could be the result of the downregulation of adenosine A1 receptors, important modulators of the glutamatergic system. Further studies are needed to investigate the effects of the zaleplon-induced increase in hippocampal glutamatergic neurotransmission and the possible involvement of the adenosine system in zaleplon’s mechanism of action.
T2  - Brain Sciences
T1  - Prolonged Zaleplon Treatment Increases the Expression of Proteins Involved in GABAergic and Glutamatergic Signaling in the Rat Hippocampus
VL  - 13
IS  - 12
SP  - 1707
DO  - 10.3390/brainsci13121707
ER  - 

@article{
author = "Martinović, Jelena and Samardžić, Janko and Zarić Kontić, Marina and Ivković, Sanja and Dacić, Sanja and Major, Tamara and Radosavljević, Milica and Svob Strac, Dubravka",
year = "2023",
abstract = "Zaleplon is a positive allosteric modulator of the γ-aminobutyric acid (GABA)A receptor approved for the short-term treatment of insomnia. Previous publications on zaleplon have not addressed the proteins involved in its mechanism of action but have mostly referred to behavioral or pharmacological studies. Since both GABAergic and glutamatergic signaling have been shown to regulate wakefulness and sleep, we examined the effects of prolonged zaleplon treatment (0.625 mg/kg for 5 days) on these systems in the hippocampus of male Wistar rats. Western blot and immunohistochemical analyses showed that the upregulated components of GABAergic signaling (glutamate decarboxylase, vesicular GABA transporter, GABA, and α1 subunit of the GABAA receptor) were accompanied by increased protein levels in the glutamatergic system (vesicular glutamate transporter 1 and NR1, NR2A, and NR2B subunits of N-methyl-d-aspartate receptor). Our results, showing that zaleplon enhances GABA neurotransmission in the hippocampus, were not surprising. However, we found that treatment also increased glutamatergic signaling. This could be the result of the downregulation of adenosine A1 receptors, important modulators of the glutamatergic system. Further studies are needed to investigate the effects of the zaleplon-induced increase in hippocampal glutamatergic neurotransmission and the possible involvement of the adenosine system in zaleplon’s mechanism of action.",
journal = "Brain Sciences",
title = "Prolonged Zaleplon Treatment Increases the Expression of Proteins Involved in GABAergic and Glutamatergic Signaling in the Rat Hippocampus",
volume = "13",
number = "12",
pages = "1707",
doi = "10.3390/brainsci13121707"
}

Martinović, J., Samardžić, J., Zarić Kontić, M., Ivković, S., Dacić, S., Major, T., Radosavljević, M.,& Svob Strac, D.. (2023). Prolonged Zaleplon Treatment Increases the Expression of Proteins Involved in GABAergic and Glutamatergic Signaling in the Rat Hippocampus. in Brain Sciences, 13(12), 1707.
https://doi.org/10.3390/brainsci13121707

Martinović J, Samardžić J, Zarić Kontić M, Ivković S, Dacić S, Major T, Radosavljević M, Svob Strac D. Prolonged Zaleplon Treatment Increases the Expression of Proteins Involved in GABAergic and Glutamatergic Signaling in the Rat Hippocampus. in Brain Sciences. 2023;13(12):1707.
doi:10.3390/brainsci13121707 .

Martinović, Jelena, Samardžić, Janko, Zarić Kontić, Marina, Ivković, Sanja, Dacić, Sanja, Major, Tamara, Radosavljević, Milica, Svob Strac, Dubravka, "Prolonged Zaleplon Treatment Increases the Expression of Proteins Involved in GABAergic and Glutamatergic Signaling in the Rat Hippocampus" in Brain Sciences, 13, no. 12 (2023):1707,
https://doi.org/10.3390/brainsci13121707 . .