Long-term alprazolam treatment may cause tolerance development by modulating components of glutamatergic neurotransmission in the hippocampus of male Wistar rats
Аутори
Zarić Kontić, MarinaDragić, Milorad
Martinović, Jelena
Mihajlović, Katarina
Brkić, Željka
Mitrović, Nataša
Guševac Stojanović, Ivana
Grković, Ivana
Конференцијски прилог (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
The benzodiazepine alprazolam (ALP) is commonly prescribed to treat anxiety, panic, and sleep disorders. However, ALP is often abused for prolonged periods of time, leading to severe side effects such as tolerance, dependence, and withdrawal syndrome. Previous literature data suggest that neuroadaptive changes at synaptic receptors, such as gammaaminobutyric acid receptor type A (GABAAR) and glutamatergic receptors, may be responsible for the occurrence and development of the aforementioned side effects. Therefore, the present study investigated the potential effects of prolonged ALP treatment (2 mg/kg, ip.) on the α1-subunit containing GABAAR and components of glutamatergic neurotransmission in the hippocampus of adult male Wistar rats. The study revealed behavioral changes consistent with a possible onset of tolerance and associated changes in the GABAergic and glutamatergic systems. The primary target of ALP, the α1-subunit containing GABAAR, was decreased indicating its potential d...ownregulation by prolonged agonist (ALP) action. Considering studied glutamatergic components, an increase in NMDAR subunits, a decrease in vGlut1, and differential modulation of excitatory amino acid transporters 1 and 2 (EAAT1/2, in vivo and in vitro) were observed. These changes may all together indicate a compensatory mechanism due to the sustained suppression of glutamatergic neurons by enhanced inhibitory impulses from GABAergic neurons. The data presented provide valuable and, to our knowledge, the first information on components of glutamatergic neurotransmission after prolonged ALP treatment and their potential impact on the development of side effects. However, further research is needed to examine the observed changes in detail.
Извор:
8th Congress of Serbian neuroscience society with international participation : the book of abstracts; 31 May – 2 June; Belgrade, 2023, 60-Издавач:
- Belgrade : Serbian Neurocardiological Society
Финансирање / пројекти:
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200017 (Универзитет у Београду, Институт за нуклеарне науке Винча, Београд-Винча) (RS-MESTD-inst-2020-200017)
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200178 (Универзитет у Београду, Биолошки факултет) (RS-MESTD-inst-2020-200178)
Напомена:
- Poster Session: Bran Stimulation & Signalling, Phase Separation and Open Data
Колекције
Институција/група
VinčaTY - CONF AU - Zarić Kontić, Marina AU - Dragić, Milorad AU - Martinović, Jelena AU - Mihajlović, Katarina AU - Brkić, Željka AU - Mitrović, Nataša AU - Guševac Stojanović, Ivana AU - Grković, Ivana PY - 2023 UR - https://vinar.vin.bg.ac.rs/handle/123456789/11048 AB - The benzodiazepine alprazolam (ALP) is commonly prescribed to treat anxiety, panic, and sleep disorders. However, ALP is often abused for prolonged periods of time, leading to severe side effects such as tolerance, dependence, and withdrawal syndrome. Previous literature data suggest that neuroadaptive changes at synaptic receptors, such as gammaaminobutyric acid receptor type A (GABAAR) and glutamatergic receptors, may be responsible for the occurrence and development of the aforementioned side effects. Therefore, the present study investigated the potential effects of prolonged ALP treatment (2 mg/kg, ip.) on the α1-subunit containing GABAAR and components of glutamatergic neurotransmission in the hippocampus of adult male Wistar rats. The study revealed behavioral changes consistent with a possible onset of tolerance and associated changes in the GABAergic and glutamatergic systems. The primary target of ALP, the α1-subunit containing GABAAR, was decreased indicating its potential downregulation by prolonged agonist (ALP) action. Considering studied glutamatergic components, an increase in NMDAR subunits, a decrease in vGlut1, and differential modulation of excitatory amino acid transporters 1 and 2 (EAAT1/2, in vivo and in vitro) were observed. These changes may all together indicate a compensatory mechanism due to the sustained suppression of glutamatergic neurons by enhanced inhibitory impulses from GABAergic neurons. The data presented provide valuable and, to our knowledge, the first information on components of glutamatergic neurotransmission after prolonged ALP treatment and their potential impact on the development of side effects. However, further research is needed to examine the observed changes in detail. PB - Belgrade : Serbian Neurocardiological Society C3 - 8th Congress of Serbian neuroscience society with international participation : the book of abstracts; 31 May – 2 June; Belgrade T1 - Long-term alprazolam treatment may cause tolerance development by modulating components of glutamatergic neurotransmission in the hippocampus of male Wistar rats SP - 60 UR - https://hdl.handle.net/21.15107/rcub_vinar_11048 ER -
@conference{ author = "Zarić Kontić, Marina and Dragić, Milorad and Martinović, Jelena and Mihajlović, Katarina and Brkić, Željka and Mitrović, Nataša and Guševac Stojanović, Ivana and Grković, Ivana", year = "2023", abstract = "The benzodiazepine alprazolam (ALP) is commonly prescribed to treat anxiety, panic, and sleep disorders. However, ALP is often abused for prolonged periods of time, leading to severe side effects such as tolerance, dependence, and withdrawal syndrome. Previous literature data suggest that neuroadaptive changes at synaptic receptors, such as gammaaminobutyric acid receptor type A (GABAAR) and glutamatergic receptors, may be responsible for the occurrence and development of the aforementioned side effects. Therefore, the present study investigated the potential effects of prolonged ALP treatment (2 mg/kg, ip.) on the α1-subunit containing GABAAR and components of glutamatergic neurotransmission in the hippocampus of adult male Wistar rats. The study revealed behavioral changes consistent with a possible onset of tolerance and associated changes in the GABAergic and glutamatergic systems. The primary target of ALP, the α1-subunit containing GABAAR, was decreased indicating its potential downregulation by prolonged agonist (ALP) action. Considering studied glutamatergic components, an increase in NMDAR subunits, a decrease in vGlut1, and differential modulation of excitatory amino acid transporters 1 and 2 (EAAT1/2, in vivo and in vitro) were observed. These changes may all together indicate a compensatory mechanism due to the sustained suppression of glutamatergic neurons by enhanced inhibitory impulses from GABAergic neurons. The data presented provide valuable and, to our knowledge, the first information on components of glutamatergic neurotransmission after prolonged ALP treatment and their potential impact on the development of side effects. However, further research is needed to examine the observed changes in detail.", publisher = "Belgrade : Serbian Neurocardiological Society", journal = "8th Congress of Serbian neuroscience society with international participation : the book of abstracts; 31 May – 2 June; Belgrade", title = "Long-term alprazolam treatment may cause tolerance development by modulating components of glutamatergic neurotransmission in the hippocampus of male Wistar rats", pages = "60", url = "https://hdl.handle.net/21.15107/rcub_vinar_11048" }
Zarić Kontić, M., Dragić, M., Martinović, J., Mihajlović, K., Brkić, Ž., Mitrović, N., Guševac Stojanović, I.,& Grković, I.. (2023). Long-term alprazolam treatment may cause tolerance development by modulating components of glutamatergic neurotransmission in the hippocampus of male Wistar rats. in 8th Congress of Serbian neuroscience society with international participation : the book of abstracts; 31 May – 2 June; Belgrade Belgrade : Serbian Neurocardiological Society., 60. https://hdl.handle.net/21.15107/rcub_vinar_11048
Zarić Kontić M, Dragić M, Martinović J, Mihajlović K, Brkić Ž, Mitrović N, Guševac Stojanović I, Grković I. Long-term alprazolam treatment may cause tolerance development by modulating components of glutamatergic neurotransmission in the hippocampus of male Wistar rats. in 8th Congress of Serbian neuroscience society with international participation : the book of abstracts; 31 May – 2 June; Belgrade. 2023;:60. https://hdl.handle.net/21.15107/rcub_vinar_11048 .
Zarić Kontić, Marina, Dragić, Milorad, Martinović, Jelena, Mihajlović, Katarina, Brkić, Željka, Mitrović, Nataša, Guševac Stojanović, Ivana, Grković, Ivana, "Long-term alprazolam treatment may cause tolerance development by modulating components of glutamatergic neurotransmission in the hippocampus of male Wistar rats" in 8th Congress of Serbian neuroscience society with international participation : the book of abstracts; 31 May – 2 June; Belgrade (2023):60, https://hdl.handle.net/21.15107/rcub_vinar_11048 .