title: NPY controls fear conditioning and fear extinction by combined action on Y₁ and Y₂ receptors.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  Here we performed Pavlovian fear conditioning and extinction in NPY knockout (KO) and in NPY receptor KO mice.
  
  
  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
  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.
authors.affiliation: Department of Pharmacology, Medical University Innsbruck, Innsbruck, Austria.
authors.forename: D
authors.initials: D
authors.lastname: Verma
authors.forename: R O
authors.initials: RO
authors.lastname: Tasan
authors.forename: H
authors.initials: H
authors.lastname: Herzog
authors.forename: G
authors.initials: G
authors.lastname: Sperk
mesh_terms: D000818:Animals; D001008:Anxiety Disorders / Q000378:metabolism; D001522:Behavior, Animal; D003214:Conditioning, Classical; D004192:Discrimination, Psychological; D005108:Extinction, Psychological; D005239:Fear; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009478:Neuropeptide Y / Q000235:genetics / Q000378:metabolism*; D017476:Receptors, Neuropeptide Y / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D009478:Neuropeptide Y; C507698:Npy1r protein, mouse; D017476:Receptors, Neuropeptide Y; C095889:neuropeptide Y2 receptor