Facilitation of Contextual Fear Extinction by Orexin-1 Receptor Antagonism Is Associated with the Activation of Specific Amygdala Cell Subpopulations

Int J Neuropsychopharmacol. 2017 Aug 1;20(8):654-659. doi: 10.1093/ijnp/pyx029.

Abstract

Background: Orexins are hypothalamic neuropeptides recently involved in the regulation of emotional memory. The basolateral amygdala, an area orchestrating fear memory processes, appears to be modulated by orexin transmission during fear extinction. However, the neuronal types within the basolateral amygdala involved in this modulation remain to be elucidated.

Methods: We used retrograde tracing combined with immunofluorescence techniques in mice to identify basolateral amygdala projection neurons and cell subpopulations in this brain region influenced by orexin transmission during contextual fear extinction consolidation.

Results: Treatment with the orexin-1 receptor antagonist SB334867 increased the activity of basolateral amygdala neurons projecting to infralimbic medial prefrontal cortex during fear extinction. GABAergic interneurons expressing calbindin, but not parvalbumin, were also activated by orexin-1 receptor antagonism in the basolateral amygdala.

Conclusions: These data identify neuronal circuits and cell populations of the amygdala associated with the facilitation of fear extinction consolidation induced by the orexin-1 receptor antagonist SB334867.

Keywords: amygdala; calbindin; fear extinction; orexin; retrograde labeling.

MeSH terms

  • Animals
  • Basolateral Nuclear Complex / cytology
  • Basolateral Nuclear Complex / drug effects*
  • Basolateral Nuclear Complex / metabolism
  • Benzoxazoles / pharmacology
  • Calbindins / metabolism
  • Extinction, Psychological / drug effects*
  • Extinction, Psychological / physiology
  • Fear / drug effects*
  • Fear / physiology
  • Male
  • Memory Consolidation / drug effects
  • Memory Consolidation / physiology
  • Mice, Inbred C57BL
  • Naphthyridines
  • Neural Pathways / cytology
  • Neural Pathways / drug effects
  • Neural Pathways / metabolism
  • Neurons / cytology
  • Neurons / drug effects*
  • Neurons / metabolism
  • Orexin Receptor Antagonists / pharmacology*
  • Orexin Receptors / metabolism
  • Parvalbumins / metabolism
  • Prefrontal Cortex / cytology
  • Prefrontal Cortex / drug effects
  • Prefrontal Cortex / metabolism
  • Psychotropic Drugs / pharmacology*
  • Urea / analogs & derivatives
  • Urea / pharmacology

Substances

  • 1-(2-methylbenzoxazol-6-yl)-3-(1,5)naphthyridin-4-yl urea
  • Benzoxazoles
  • Calbindins
  • Naphthyridines
  • Orexin Receptor Antagonists
  • Orexin Receptors
  • Parvalbumins
  • Psychotropic Drugs
  • Urea