Ketamine ameliorates fear extinction learning in adolescent males via hippocampal mTOR signaling
Authors
Glavonić, Emilija
Aleksić, Minja
Francija, Ester

Mitić, Miloš

Lukić, Iva

Ivković, Sanja

Adžić, Miroslav

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Adolescence is a developmental stage characterized by impaired fear extinction learning, which is a significant contributing factor for the high incidence of fearrelated disorders observed across this period. Ketamine is a noncompetitive N-methyl D-aspartate receptor antagonist that targets glutamatergic transmission and mammalian target of rapamycin (mTOR) signaling pathway, synaptic plasticity mediators known to be involved in fear extinction processes. Therefore, we aimed to explore ketamine’s potential to boost fear extinction of adolescent males, as well as to identify the associated molecular mechanisms. Adolescent male mice (C57BL/6) received an i.p. ketamine injection (10 mg/kg) 1h prior to each cued fear extinction session for 4 consecutive days. Protein expression levels of synaptic plasticity markers in hippocampal synaptosomal fractions were subsequently detected by Western blot analysis. Our results revealed that ketamine significantly improved overall fear extinction lear...ning, as well as extinction memory consolidation/retention. Our data also showed that ketamine upregulated protein kinase B (Akt), mTOR and glutamate receptor 1 (GluR1) protein levels in the hippocampus. Interestingly, we detected no changes in the levels of extracellular signal-regulated kinase 1/2. These results suggest that ketamine ameliorates longterm fear extinction of adolescent males via hippocampal Akt-mTOR-GluR1 signaling, highlighting this pathway as an important therapeutic target for improving extinction learning in the adolescent population.
Source:
8th Congress of Serbian neuroscience society with international participation : the book of abstracts; 31 May – 2 June; Belgrade, 2023, 82-Publisher:
- Belgrade : Serbian Neuroscience Society
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- Poster Session: Brain Metabolism & Dietary Interventions
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VinčaTY - CONF AU - Glavonić, Emilija AU - Aleksić, Minja AU - Francija, Ester AU - Mitić, Miloš AU - Lukić, Iva AU - Ivković, Sanja AU - Adžić, Miroslav PY - 2023 UR - https://vinar.vin.bg.ac.rs/handle/123456789/11051 AB - Adolescence is a developmental stage characterized by impaired fear extinction learning, which is a significant contributing factor for the high incidence of fearrelated disorders observed across this period. Ketamine is a noncompetitive N-methyl D-aspartate receptor antagonist that targets glutamatergic transmission and mammalian target of rapamycin (mTOR) signaling pathway, synaptic plasticity mediators known to be involved in fear extinction processes. Therefore, we aimed to explore ketamine’s potential to boost fear extinction of adolescent males, as well as to identify the associated molecular mechanisms. Adolescent male mice (C57BL/6) received an i.p. ketamine injection (10 mg/kg) 1h prior to each cued fear extinction session for 4 consecutive days. Protein expression levels of synaptic plasticity markers in hippocampal synaptosomal fractions were subsequently detected by Western blot analysis. Our results revealed that ketamine significantly improved overall fear extinction learning, as well as extinction memory consolidation/retention. Our data also showed that ketamine upregulated protein kinase B (Akt), mTOR and glutamate receptor 1 (GluR1) protein levels in the hippocampus. Interestingly, we detected no changes in the levels of extracellular signal-regulated kinase 1/2. These results suggest that ketamine ameliorates longterm fear extinction of adolescent males via hippocampal Akt-mTOR-GluR1 signaling, highlighting this pathway as an important therapeutic target for improving extinction learning in the adolescent population. PB - Belgrade : Serbian Neuroscience Society C3 - 8th Congress of Serbian neuroscience society with international participation : the book of abstracts; 31 May – 2 June; Belgrade T1 - Ketamine ameliorates fear extinction learning in adolescent males via hippocampal mTOR signaling SP - 82 UR - https://hdl.handle.net/21.15107/rcub_vinar_11051 ER -
@conference{ author = "Glavonić, Emilija and Aleksić, Minja and Francija, Ester and Mitić, Miloš and Lukić, Iva and Ivković, Sanja and Adžić, Miroslav", year = "2023", abstract = "Adolescence is a developmental stage characterized by impaired fear extinction learning, which is a significant contributing factor for the high incidence of fearrelated disorders observed across this period. Ketamine is a noncompetitive N-methyl D-aspartate receptor antagonist that targets glutamatergic transmission and mammalian target of rapamycin (mTOR) signaling pathway, synaptic plasticity mediators known to be involved in fear extinction processes. Therefore, we aimed to explore ketamine’s potential to boost fear extinction of adolescent males, as well as to identify the associated molecular mechanisms. Adolescent male mice (C57BL/6) received an i.p. ketamine injection (10 mg/kg) 1h prior to each cued fear extinction session for 4 consecutive days. Protein expression levels of synaptic plasticity markers in hippocampal synaptosomal fractions were subsequently detected by Western blot analysis. Our results revealed that ketamine significantly improved overall fear extinction learning, as well as extinction memory consolidation/retention. Our data also showed that ketamine upregulated protein kinase B (Akt), mTOR and glutamate receptor 1 (GluR1) protein levels in the hippocampus. Interestingly, we detected no changes in the levels of extracellular signal-regulated kinase 1/2. These results suggest that ketamine ameliorates longterm fear extinction of adolescent males via hippocampal Akt-mTOR-GluR1 signaling, highlighting this pathway as an important therapeutic target for improving extinction learning in the adolescent population.", publisher = "Belgrade : Serbian Neuroscience Society", journal = "8th Congress of Serbian neuroscience society with international participation : the book of abstracts; 31 May – 2 June; Belgrade", title = "Ketamine ameliorates fear extinction learning in adolescent males via hippocampal mTOR signaling", pages = "82", url = "https://hdl.handle.net/21.15107/rcub_vinar_11051" }
Glavonić, E., Aleksić, M., Francija, E., Mitić, M., Lukić, I., Ivković, S.,& Adžić, M.. (2023). Ketamine ameliorates fear extinction learning in adolescent males via hippocampal mTOR signaling. in 8th Congress of Serbian neuroscience society with international participation : the book of abstracts; 31 May – 2 June; Belgrade Belgrade : Serbian Neuroscience Society., 82. https://hdl.handle.net/21.15107/rcub_vinar_11051
Glavonić E, Aleksić M, Francija E, Mitić M, Lukić I, Ivković S, Adžić M. Ketamine ameliorates fear extinction learning in adolescent males via hippocampal mTOR signaling. in 8th Congress of Serbian neuroscience society with international participation : the book of abstracts; 31 May – 2 June; Belgrade. 2023;:82. https://hdl.handle.net/21.15107/rcub_vinar_11051 .
Glavonić, Emilija, Aleksić, Minja, Francija, Ester, Mitić, Miloš, Lukić, Iva, Ivković, Sanja, Adžić, Miroslav, "Ketamine ameliorates fear extinction learning in adolescent males via hippocampal mTOR signaling" in 8th Congress of Serbian neuroscience society with international participation : the book of abstracts; 31 May – 2 June; Belgrade (2023):82, https://hdl.handle.net/21.15107/rcub_vinar_11051 .