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Br J Pharmacol. 2012 Jun;166(4):1461-73. doi: 10.1111/j.1476-5381.2012.01872.x.

NPY controls fear conditioning and fear extinction by combined action on Y₁ and Y₂ receptors.

Author information

1
Department of Pharmacology, Medical University Innsbruck, Innsbruck, Austria.

Abstract

BACKGROUND AND PURPOSE:

Neuropeptide Y (NPY) and its receptors have been implicated in the control of emotional-affective processing, but the mechanism is unclear. While it is increasingly evident that stimulation of Y₁ and inhibition of Y₂ receptors produce prominent anxiolytic and antidepressant effects, the contribution of the individual NPY receptor subtypes in the acquisition and extinction of learned fear are unknown.

EXPERIMENTAL APPROACH:

Here we performed Pavlovian fear conditioning and extinction in NPY knockout (KO) and in NPY receptor KO mice.

KEY RESULTS:

NPY KO mice display a dramatically accelerated acquisition of conditioned fear. Deletion of Y₁ receptors revealed only a moderately accelerated acquisition of conditioned fear, while lack of Y₂ receptors was without any effect on fear learning. However, the strong phenotype seen in NPY KO mice was reproduced in mice lacking both Y₁ and Y₂ receptors. In addition, NPY KO mice showed excessive recall of conditioned fear and impaired fear extinction. This behaviour was replicated only after deletion of both Y₁ and Y₂ receptors. In Y₁ receptor single KO mice, fear extinction was delayed and was unchanged in Y₂ receptor KO mice. Deletion of NPY and particularly Y₂ receptors resulted in a generalization of conditioned fear.

CONCLUSIONS AND IMPLICATIONS:

Our data demonstrate that NPY delays the acquisition, reduces the expression of conditioned fear while promoting fear extinction. Although these effects appear to be primarily mediated by Y₁ receptors, the pronounced phenotype of Y₁Y₂ receptor double KO mice suggests a synergistic role of Y₂ receptors in fear acquisition and in fear extinction.

PMID:
22289084
PMCID:
PMC3401902
DOI:
10.1111/j.1476-5381.2012.01872.x
[Indexed for MEDLINE]
Free PMC Article

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