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The role of NPY in expression and extinction of conditioned fear


Neuropeptide Y is a highly conserved 36 amino acid peptide that is widely distributed in the peripheral and central nervous systems. Besides its functions in various metabolic processes, NPY has attracted considerable attention in modulating emotional-affective behavior. NPY exerts a solid anxiolytic effect most likely mediated by Y1 receptors, whereas stimulation of predominantly pre-synaptic Y2 receptors results in increased anxiety. However, little is known about an involvement of NPY in processing of fear.


The current study aims to elucidate the role of NPY in Pavlovian fear conditioning, a simple form of associative learning. NPY knockout (NPY KO) mice as well as knockout mice for the different NPY receptors (Y1, Y2, Y4 and Y1/Y2 double KO) were subjected to a delay fear-conditioning paradigm (5 presentations of a tone co-terminating with a mild electric foot shock, 0.7 mA). Extinction learning was performed the following day by repetitive exposure to the tone (40 presentations) in the absence of a foot shock.


Compared to wild-type controls, NPY KO mice revealed faster acquisition and augmented expression of conditioned fear. Baseline freezing was increased on retention/extinction day, indicating a generalization of conditioned fear. Moreover, NPY KO mice displayed a pronounced deficit in the extinction of fear memory. Within sessions, extinction as well as extinction recall were significantly impaired in NPY KO mice. Conversely, acquisition of fear was reduced in Y2 KO mice. Interestingly, no corresponding changes in extinction of conditioned fear were seen in Y2 KO mice. However, Y4 KO mice exhibited an impairment in fear extinction, similar to the one seen in NPY KO mice.


Our data indicate that NPY has a protective role in the acquisition of fear memories. In addition, it facilitates extinction of conditioned fear. Results from Y receptor KO mice suggest that Y1 and Y2 receptors are the most likely candidates for modulating the acquisition of fear, whereas for extinction a concerted action of Y1 and Y4 receptors seems to be conceivable.

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Correspondence to Ramon O Tasan.

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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution License ( ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Verma, D., Tasan, R.O., Herzog, H. et al. The role of NPY in expression and extinction of conditioned fear. BMC Pharmacol 9 (Suppl 2), A33 (2009).

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