Toth, Iulia and Dietz, Monika and Peterlik, Daniel and Huber, Sabine E. and Fendt, Markus and Neumann, Inga D. and Flor, Peter J. and Slattery, David A. (2012) Pharmacological interference with metabotropic glutamate receptor subtype 7 but not subtype 5 differentially affects within- and between-session extinction of Pavlovian conditioned fear. NEUROPHARMACOLOGY, 62 (4). pp. 1619-1626. ISSN 0028-3908, 1873-7064
Full text not available from this repository. (Request a copy)Abstract
Fear extinction is defined as the attenuation of a conditioned-fear memory by re-exposing animals to the conditioned stimulus without the aversive stimulus. This process is known to be effectively enhanced via administration of D-cycloserine (DCS), a partial NMDA-receptor agonist. However, other glutamatergic mechanisms, such as interference with metabotropic glutamate receptor (mGluR) subtypes 5 and 7 in the extinction of aversive memories are insufficiently understood. Using the allosteric mGluR5 receptor antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP), the mGluR7 allosteric agonist N,N'-dibenzyhydryl-ethane-1,2-diamine dihydrochloride (AMN082), and DCS for comparison, we aimed to study how pharmacological blockade of mGluR5 and activation of mGluR7 influenced within- and between-session conditioned-fear extinction training and extinction retention in rats. We show that when injected before extinction training, mGluR7 activation with AMN082 enhanced freezing and thereby attenuated within-session fear extinction, whereas both DCS and the mGluR5 receptor antagonist MPEP had no effect on this process. However, these differential drug effects were not long lasting, as no difference in extinction retention were observed 24 h later. Therefore, we assessed whether the compounds affect 24 h consolidation of extinction training following incomplete extinction training (between-session extinction). Similar to DCS, AMN082- but not MPEP-treated rats showed facilitated extinction retention, as exhibited by decreased freezing. Finally, using fluoxetine, we provide evidence that the effect of AMN082 on between-session extinction retention is most likely not via increasing 5-HT transmission. These findings demonstrate that mGluR7 activation differentially modulates conditioned-fear extinction, in dependence on the protocol employed, and suggests drugs with AMN082-like mechanisms as potential add-on drugs following exposure-based psychotherapy for fear-related human disorders. (c) 2011 Elsevier Ltd. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CYCLOSERINE FACILITATES EXTINCTION; CEREBROCORTICAL NERVE-TERMINALS; PLACE PREFERENCE; PRESYNAPTIC LOCALIZATION; POTENTIATED STARTLE; MGLUR5 ANTAGONISTS; RAT HIPPOCAMPUS; ETHANOL-SEEKING; COCAINE; MICE; AMN082; DCS; Fear extinction; L-glutamate; MPEP; mGluR5; mGluR7 |
| Subjects: | 500 Science > 570 Life sciences 500 Science > 590 Zoological sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Zoologie Biology, Preclinical Medicine > Institut für Zoologie > Molecular and Cellular Neurobiology (Prof. Dr. Peter J. Flor) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 19 May 2020 08:42 |
| Last Modified: | 19 May 2020 08:42 |
| URI: | https://pred.uni-regensburg.de/id/eprint/19166 |
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