Neuropeptide Y reduces expression of social fear via simultaneous activation of Y1 and Y2 receptors.
Social fear
extinction
fear expression
fear learning
neuropeptide Y
social investigation
Journal
Journal of psychopharmacology (Oxford, England)
ISSN: 1461-7285
Titre abrégé: J Psychopharmacol
Pays: United States
ID NLM: 8907828
Informations de publication
Date de publication:
12 2019
12 2019
Historique:
pubmed:
23
7
2019
medline:
15
8
2020
entrez:
23
7
2019
Statut:
ppublish
Résumé
Neuropeptide Y (NPY) has anxiolytic effects and facilitates extinction of cued and contextual fear in rodents, thereby acting as a resilience factor against exaggerated fear responses after adverse events. We investigated whether NPY influences acquisition, expression and extinction of social fear in a mouse model of social fear conditioning (SFC). NPY was administered intracerebroventricularly before SFC or before social fear extinction with or without prior administration of Y1 and/or Y2 receptor antagonists. We show that NPY affects SFC-induced social fear in a time point-dependent manner. When administered before SFC, NPY did not affect acquisition, expression and extinction of social fear. However, when administered before social fear extinction, NPY reduced expression of social fear via simultaneous activation of Y1 and Y2 receptors. As such, neither the Y1 receptor antagonist BIBO3304 trifluoroacetate nor the Y2 receptor antagonist BIIE0246 was able to block the effects of NPY completely. However, when administered in combination, they completely blocked the effects of NPY on social fear expression. These findings have important clinical implications, as they suggest that although medication strategies aimed at increasing brain NPY activity are unlikely to prevent the formation of aversive memories after a traumatic social experience, they might improve the recovery from a traumatic social experience by reducing the expression of social fear.
Sections du résumé
BACKGROUND
Neuropeptide Y (NPY) has anxiolytic effects and facilitates extinction of cued and contextual fear in rodents, thereby acting as a resilience factor against exaggerated fear responses after adverse events. We investigated whether NPY influences acquisition, expression and extinction of social fear in a mouse model of social fear conditioning (SFC).
METHODS
NPY was administered intracerebroventricularly before SFC or before social fear extinction with or without prior administration of Y1 and/or Y2 receptor antagonists.
RESULTS
We show that NPY affects SFC-induced social fear in a time point-dependent manner. When administered before SFC, NPY did not affect acquisition, expression and extinction of social fear. However, when administered before social fear extinction, NPY reduced expression of social fear via simultaneous activation of Y1 and Y2 receptors. As such, neither the Y1 receptor antagonist BIBO3304 trifluoroacetate nor the Y2 receptor antagonist BIIE0246 was able to block the effects of NPY completely. However, when administered in combination, they completely blocked the effects of NPY on social fear expression.
CONCLUSIONS
These findings have important clinical implications, as they suggest that although medication strategies aimed at increasing brain NPY activity are unlikely to prevent the formation of aversive memories after a traumatic social experience, they might improve the recovery from a traumatic social experience by reducing the expression of social fear.
Identifiants
pubmed: 31328614
doi: 10.1177/0269881119862529
pmc: PMC6854880
doi:
Substances chimiques
Benzazepines
0
Neuropeptide Y
0
Receptors, Neuropeptide Y
0
neuropeptide Y-Y1 receptor
0
neuropeptide Y2 receptor
0
Arginine
94ZLA3W45F
BIIE 0246
N3Z657H81X
BIBO 3304
O35HK034KO
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1533-1539Références
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