Please use this identifier to cite or link to this item: https://biore.bio.bg.ac.rs/handle/123456789/5354
Title: Prolonged Alprazolam Treatment Alters Components of Glutamatergic Neurotransmission in the Hippocampus of Male Wistar Rats—The Neuroadaptive Changes following Long-Term Benzodiazepine (Mis)Use
Authors: Zarić Kontić, Marina
Dragić, Milorad 
Martinović, Jelena
Mihajlović, Katarina 
Brkić, Željka
Mitrović, Nataša
Grković, Ivana
Keywords: Alprazolam;Benzodiazepines;Hippocampus;N-Methyl-d-aspartate receptor;Gammaaminobutyric acid receptor type A;Excitatory amino acid transporters ½
Issue Date: 21-Feb-2023
Rank: M21
Publisher: MDPI
Journal: Pharmaceuticals
Volume: 16
Issue: 3
Start page: 331
Abstract: 
Alprazolam (ALP), a benzodiazepine (BDZ) used to treat anxiety, panic, and sleep disorders, is one of the most prescribed psychotropic drugs worldwide. The side effects associated with long-term (mis)use of ALP have become a major challenge in pharmacotherapy, emphasizing the unmet need to further investigate their underlying molecular mechanisms. Prolonged BDZ exposure may induce adaptive changes in the function of several receptors, including the primary target, gammaaminobutyric acid receptor type A (GABAAR), but also other neurotransmitter receptors such as glutamatergic. The present study investigated the potential effects of prolonged ALP treatment on components of glutamatergic neurotransmission, with special emphasis on N-Methyl-D-aspartate receptor (NMDAR) in the hippocampus of adult male Wistar rats. The study revealed behavioral changes consistent with potential onset of tolerance and involvement of the glutamatergic system in its development. Specifically, an increase in NMDAR subunits (NR1, NR2A, NR2B), a decrease in vesicular glutamate transporter 1 (vGlut1), and differential modulation of excitatory amino acid transporters 1 and 2 (EAAT1/2, in vivo and in vitro) were observed, alongside a decrease in α1-containing GABAAR following the treatment. By describing the development of compensatory actions in the glutamatergic system, the present study provides valuable information on neuroadaptive mechanisms following prolonged ALP intake.
URI: https://biore.bio.bg.ac.rs/handle/123456789/5354
ISSN: 1424-8247
DOI: 10.3390/ph16030331
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