Neuropeptide Y in the amygdala induces long-term resilience to stress-induced reductions in social responses but not hypothalamic-adrenal- pituitary axis activity or hyperthermia

Tammy J. Sajdyk, Philip L. Johnson, Randy J. Leitermann, Stephanie D. Fitz, Amy Dietrich, Michelle Morin, Donald R. Gehlert, Janice H. Urban, Anantha Shekhar

Research output: Contribution to journalArticle

97 Scopus citations


Resilience to mental and physical stress is a key determinant for the survival and functioning of mammals. Although the importance of stress resilience has been recognized, the underlying neural mediators have not yet been identified. Neuropeptide Y (NPY) is a peptide known for its anti-anxiety-like effects mediated via the amygdala. The results of our current study demonstrate, for the first time that repeated administration of NPY directly into the basolateral nucleus of the amygdala (BLA) produces selective stress-resilient behavioral responses to an acute restraint challenge as measured in the social interaction test, but has no effect on hypothalamic-adrenal-pituitary axis activity or stress-induced hyperthermia. More importantly, the resilient behaviors observed in the NPY-treated animals were present for up to 8 weeks. Antagonizing the activity of calcineurin, a protein phosphatase involved in neuronal remodeling and present in NPY receptor containing neurons within the BLA, blocked the development of long-term, but not the acute increases in social interaction responses induced by NPY administration. This suggests that the NPY-induced long-term behavioral resilience to restraint stress may occur via mechanisms involving neuronal plasticity. These studies suggest one putative physiologic mechanism underlying stress resilience and could identify novel targets for development of therapies that can augment the ability to cope with stress.

Original languageEnglish (US)
Pages (from-to)893-903
Number of pages11
JournalJournal of Neuroscience
Issue number4
StatePublished - Jan 23 2008



  • Amygdala
  • Anxiety
  • Anxiolytic
  • Autonomic
  • BNST
  • CRF
  • CRH
  • Hypothalamus
  • Neuropeptide
  • NPY
  • Septum

ASJC Scopus subject areas

  • Neuroscience(all)

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