Tags

Type your tag names separated by a space and hit enter

Augmentation of fear extinction by D-cycloserine is blocked by proteasome inhibitors.
Neuropsychopharmacology. 2008 Dec; 33(13):3085-95.N

Abstract

D-Cycloserine (DCS) has been shown to facilitate extinction of conditioned fear in rats and to improve fear reduction of social phobia and fear of heights in human studies. Here, we investigate the mechanism of DCS effect by measuring internalized GluR1 and GluR2 using cell-surface biotinylation techniques. DCS selectively increased NMDA receptor-mediated synaptic response without affecting AMPA receptor-mediated synaptic response. Low-frequency stimulation (LFS) when applied in the presence of DCS induced GluR1 and GluR2 internalization in the amygdala slices. Proteasome inhibitors block DCS facilitation of LFS-induced depotentiation and a reduction in surface levels of GluR1 and GluR2. Furthermore, DCS in combination with LFS reduced cellular levels of PSD-95 and synapse-associated protein 97 (SAP97), which were also blocked by proteasome inhibitors. In the in vivo experiments, DCS-induced reduction of fear-potentiated startle and reversal of conditioning-induced increase in surface expression of GluR1 were blocked by proteasome inhibitors. DCS-treated rats fail to exhibit reinstatement after US-alone presentations. These results suggest that DCS facilitates receptor internalization in the presence of extinction training, resulting in augmented reduction of startle potentiation.

Links

Publisher Full Text (DOI)

Authors+Show Affiliations

Mao SC
Institute of Basic Medical Sciences, National Cheng-Kung University, Tainan, Taiwan.
Lin HC
No affiliation info available
Gean PW
No affiliation info available

MeSH

Adaptor Proteins, Signal TransducingAmygdalaAnimalsAntimetabolitesCycloserineDisks Large Homolog 4 ProteinElectric StimulationEndocytosisEnzyme InhibitorsExcitatory Amino Acid AgonistsExtinction, PsychologicalFearIntracellular Signaling Peptides and ProteinsMaleMembrane ProteinsOrgan Culture TechniquesProteasome Endopeptidase ComplexProteasome InhibitorsProtein TransportRatsRats, Sprague-DawleyReceptors, AMPAReflex, StartleSynaptic Transmission

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18368037

Citation

Mao, Sheng-Chun, et al. "Augmentation of Fear Extinction By D-cycloserine Is Blocked By Proteasome Inhibitors." Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology, vol. 33, no. 13, 2008, pp. 3085-95.
Mao SC, Lin HC, Gean PW. Augmentation of fear extinction by D-cycloserine is blocked by proteasome inhibitors. Neuropsychopharmacology. 2008;33(13):3085-95.
Mao, S. C., Lin, H. C., & Gean, P. W. (2008). Augmentation of fear extinction by D-cycloserine is blocked by proteasome inhibitors. Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology, 33(13), 3085-95. https://doi.org/10.1038/npp.2008.30
Mao SC, Lin HC, Gean PW. Augmentation of Fear Extinction By D-cycloserine Is Blocked By Proteasome Inhibitors. Neuropsychopharmacology. 2008;33(13):3085-95. PubMed PMID: 18368037.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Augmentation of fear extinction by D-cycloserine is blocked by proteasome inhibitors. AU - Mao,Sheng-Chun, AU - Lin,Hui-Ching, AU - Gean,Po-Wu, Y1 - 2008/03/26/ PY - 2008/3/28/pubmed PY - 2009/2/20/medline PY - 2008/3/28/entrez SP - 3085 EP - 95 JF - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology JO - Neuropsychopharmacology VL - 33 IS - 13 N2 - D-Cycloserine (DCS) has been shown to facilitate extinction of conditioned fear in rats and to improve fear reduction of social phobia and fear of heights in human studies. Here, we investigate the mechanism of DCS effect by measuring internalized GluR1 and GluR2 using cell-surface biotinylation techniques. DCS selectively increased NMDA receptor-mediated synaptic response without affecting AMPA receptor-mediated synaptic response. Low-frequency stimulation (LFS) when applied in the presence of DCS induced GluR1 and GluR2 internalization in the amygdala slices. Proteasome inhibitors block DCS facilitation of LFS-induced depotentiation and a reduction in surface levels of GluR1 and GluR2. Furthermore, DCS in combination with LFS reduced cellular levels of PSD-95 and synapse-associated protein 97 (SAP97), which were also blocked by proteasome inhibitors. In the in vivo experiments, DCS-induced reduction of fear-potentiated startle and reversal of conditioning-induced increase in surface expression of GluR1 were blocked by proteasome inhibitors. DCS-treated rats fail to exhibit reinstatement after US-alone presentations. These results suggest that DCS facilitates receptor internalization in the presence of extinction training, resulting in augmented reduction of startle potentiation. SN - 1740-634X UR - https://www.unboundmedicine.com/medline/citation/18368037/Augmentation_of_fear_extinction_by_D_cycloserine_is_blocked_by_proteasome_inhibitors_ DB - PRIME DP - Unbound Medicine ER -