title: Role of NPY Y1 receptor on acquisition, consolidation and extinction on contextual fear conditioning: dissociation between anxiety, locomotion and non-emotional memory behavior.
abstract: Neuropeptide Y (NPY) is the most abundant peptide in the central nervous system (CNS) and is densely localized in the brain regions involved in stress, memory, fear and anxiety. Although previous research supports a role for NPY in the mediation of rodent and human emotional behavior, there is currently a lack of information on the effects of low doses of NPY that could have a potential therapeutic advantage, minimizing side-effects such as cognition impairment or sedation. Herein, we assessed the effects of intracerebroventricular (i.c.v.) administration of low doses of NPY, and of the Y1-agonist Leu31Pro34-NPY (LP-NPY) on contextual fear conditioning (CFC), as they have no effect on unconditioned anxiety-like, locomotor activity and non-emotional memory. NPY (3 pmol) and LP-NPY (1 pmol) inhibited freezing behavior when administered in the acquisition or consolidation stages, indicating a reduction of fear. When injected in the extinction phase, only NPY inhibited freezing behavior on CFC. Pre-treatment with the Y1-antagonist BIBO3304 before NPY and LP-NPY was able to prevent the inhibition of fear responses induced by both NPY agonists. Taken together, our results demonstrate robust fear-inhibiting effects of i.c.v. injection of NPY on contextual fear conditioning in rats, a response that is mediated, at least in part, by the Y1 receptor. Moreover, these treatments were unable to change locomotor activity or to show an anxiolytic-like effect, as evaluated in an open-field and an elevated plus-maze. This specific fear reduction effect may underlie resilience systems in the CNS and has potential therapeutic relevance in PTSD.
authors.affiliation: Laboratory of Neuropharmacology, Department of Pharmacology, CCB, Federal University of Santa Catarina - UFSC, Florianópolis, SC 88049-970, Brazil.
authors.forename: Gilliard
authors.initials: G
authors.lastname: Lach
authors.forename: Thereza Christina Monteiro
authors.initials: TC
authors.lastname: de Lima
mesh_terms: D000818:Animals; D001007:Anxiety / Q000378:metabolism* / Q000503:physiopathology / Q000523:psychology; D001245:Association Learning / Q000187:drug effects / Q000502:physiology; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology*; D005108:Extinction, Psychological / Q000187:drug effects / Q000502:physiology*; D005239:Fear / Q000187:drug effects / Q000502:physiology*; D008124:Locomotion / Q000187:drug effects / Q000502:physiology*; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology*; D009478:Neuropeptide Y / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017476:Receptors, Neuropeptide Y / Q000819:agonists / Q000378:metabolism*
chemical_list: D009478:Neuropeptide Y; D017476:Receptors, Neuropeptide Y; C097212:neuropeptide Y-Y1 receptor