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Augmentation of fear extinction by infusion of glycine transporter blockers into the amygdala.
Mol Pharmacol. 2009 Aug; 76(2):369-78.MP

Abstract

It is known that fear extinction is blocked by the N-methyl D-aspartate (NMDA) receptor antagonist. In this study, we investigate whether extinction could be facilitated by the enhancement of NMDA response, achieved by the blocking of glycine transporters. In amygdala slices, NMDA at a concentration that normally does not have a long-term effect was found to reduce the cellular levels of postsynaptic density protein 95 and synapse-associated protein 97, in addition to the surface expression of GluR1/2, in the presence of a glycine transporter blocker, N[3-(4-fluorophenil)-3-(4'-phenilphenoxy)] propylsarcosine (NFPS). In in vivo experiments, extinction training applied 24 h after conditioning reduced startle potentiation without influencing the conditioning-induced increase in the surface expression of GluR1/2. However, NFPS augmented extinction and reversed the conditioning-induced increase in GluR1/2 when infused bilaterally into the amygdala before extinction training. The effects of NFPS were therefore blocked by the NMDA antagonist. In parallel, NFPS treatment in conjunction with extinction reversed the conditioning-induced alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/NMDA ratio. In behavioral tests, Tat-GluR2(3Y), a synthetic peptide that has been shown to block AMPA receptor endocytosis, inhibited only the additional reduction caused by NFPS treatment, rather than returning the fear potentiation levels to those of fear-conditioned animals that did not undergo extinction. These results suggest that NFPS in combination with extinction training reverses GluR1/2 surface expression and thus augments the extinction of conditioned fear.

Authors+Show Affiliations

Institute of Basic Medical Sciences and Department of Pharmacology, Center for Gene Regulation and Signal Transduction Research, National Cheng-Kung University, Tainan, Taiwan.No affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

19411609

Citation

Mao, Sheng-Chun, et al. "Augmentation of Fear Extinction By Infusion of Glycine Transporter Blockers Into the Amygdala." Molecular Pharmacology, vol. 76, no. 2, 2009, pp. 369-78.
Mao SC, Lin HC, Gean PW. Augmentation of fear extinction by infusion of glycine transporter blockers into the amygdala. Mol Pharmacol. 2009;76(2):369-78.
Mao, S. C., Lin, H. C., & Gean, P. W. (2009). Augmentation of fear extinction by infusion of glycine transporter blockers into the amygdala. Molecular Pharmacology, 76(2), 369-78. https://doi.org/10.1124/mol.108.053728
Mao SC, Lin HC, Gean PW. Augmentation of Fear Extinction By Infusion of Glycine Transporter Blockers Into the Amygdala. Mol Pharmacol. 2009;76(2):369-78. PubMed PMID: 19411609.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Augmentation of fear extinction by infusion of glycine transporter blockers into the amygdala. AU - Mao,Sheng-Chun, AU - Lin,Hui-Ching, AU - Gean,Po-Wu, Y1 - 2009/05/01/ PY - 2009/5/5/entrez PY - 2009/5/5/pubmed PY - 2009/8/18/medline SP - 369 EP - 78 JF - Molecular pharmacology JO - Mol Pharmacol VL - 76 IS - 2 N2 - It is known that fear extinction is blocked by the N-methyl D-aspartate (NMDA) receptor antagonist. In this study, we investigate whether extinction could be facilitated by the enhancement of NMDA response, achieved by the blocking of glycine transporters. In amygdala slices, NMDA at a concentration that normally does not have a long-term effect was found to reduce the cellular levels of postsynaptic density protein 95 and synapse-associated protein 97, in addition to the surface expression of GluR1/2, in the presence of a glycine transporter blocker, N[3-(4-fluorophenil)-3-(4'-phenilphenoxy)] propylsarcosine (NFPS). In in vivo experiments, extinction training applied 24 h after conditioning reduced startle potentiation without influencing the conditioning-induced increase in the surface expression of GluR1/2. However, NFPS augmented extinction and reversed the conditioning-induced increase in GluR1/2 when infused bilaterally into the amygdala before extinction training. The effects of NFPS were therefore blocked by the NMDA antagonist. In parallel, NFPS treatment in conjunction with extinction reversed the conditioning-induced alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/NMDA ratio. In behavioral tests, Tat-GluR2(3Y), a synthetic peptide that has been shown to block AMPA receptor endocytosis, inhibited only the additional reduction caused by NFPS treatment, rather than returning the fear potentiation levels to those of fear-conditioned animals that did not undergo extinction. These results suggest that NFPS in combination with extinction training reverses GluR1/2 surface expression and thus augments the extinction of conditioned fear. SN - 1521-0111 UR - https://www.unboundmedicine.com/medline/citation/19411609/Augmentation_of_fear_extinction_by_infusion_of_glycine_transporter_blockers_into_the_amygdala_ L2 - http://molpharm.aspetjournals.org/cgi/pmidlookup?view=long&pmid=19411609 DB - PRIME DP - Unbound Medicine ER -