Pharmacological interference with metabotropic glutamate receptor subtype 7 but not subtype 5 differentially affects within- and between-session extinction of Pavlovian conditioned fear.
Tools
Tools
Bahe, Amine, Toth, Iulia, Fendt, Markus, Neumann, Inga D, 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. Neuropsychopharmacology, 62 (4). pp. 1619-1626. ISSN 0028-3908
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, the role of other glutamatergic systems, such as the metabotropic glutamate receptors (mGluR) 5 and mGluR7 in the extinction of aversive memories is insufficiently understood. Using the mGluR5 receptor antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP) and the mGluR7 allosteric agonist N,N'-dibenzyhydryl-ethane-1,2-diamine dihydrochloride (AMN082), we aimed to study how mGluR5 and mGluR7 pharmacological modulation may influence within- and between-session conditioned-fear extinction in rats. We show that when injected before extinction, the mGluR5 receptor antagonist MPEP, facilitates within-session extinction. In contrast, we demonstrate that mGluR7 activation with AMN082 delays within-session fear extinction. However, when assessed 24h later, neither compound affected consolidation, possibly due to almost complete within-session extinction in all groups. Therefore, we assessed whether the compounds affected 24h consolidation following an incomplete extinction training session. Similar to DCS, and as shown previously shown, AMN082-treated rats showed facilitated extinction retention, as exhibited by decreased freezing. In contrast, MPEP had no effect on between-session extinction. These findings clearly show that mGluR5 and mGluR7 differentially and critically modulate conditioned-fear extinction. Moreover, they suggest that therapeutic agents acting at these receptors should be given during different phases of extinction of fear-related disorders.
| Item Type: | Article |
|---|---|
| Related URLs: | |
| Additional Information: | author can archive post-print (ie final draft post-refereeing); Publisher's version/PDF cannot be used |
| Keywords: | AMN082, DCS, Fear extinction, L-glutamate, MPEP, mGluR5, mGluR7 |
| Related URLs: | |
| Date Deposited: | 13 Oct 2015 13:15 |
| Last Modified: | 13 Oct 2015 13:15 |
| URI: | https://oak.novartis.com/id/eprint/3787 |