Noradrenergic Regulation of Central Amygdala in Aversive Pavlovian-to-Instrumental Transfer

eNeuro. 2017 Oct 24;4(5):ENEURO.0224-17.2017. doi: 10.1523/ENEURO.0224-17.2017. eCollection 2017 Sep-Oct.


The neural mechanisms through which a Pavlovian conditioned stimulus (CS) elicits innate defense responses are well understood. But a Pavlovian CS can also invigorate ongoing instrumental responding, as shown by studies of aversive Pavlovian-to-instrumental transfer (PIT). While the neural circuitry of appetitive PIT has been studied extensively, little is known about the brain mechanisms of aversive PIT. We recently showed the central amygdala (CeA) is essential for aversive PIT. In the current studies, using pharmacology and designer receptors in rodents, we demonstrate that noradrenergic (NE) activity negatively regulates PIT via brainstem locus coeruleus (LC) activity and LC projections to CeA. Our results provide evidence for a novel pathway through which response modulation occurs between brainstem neuromodulatory systems and CeA to invigorate adaptive behavior in the face of threat.

Keywords: PIT; central amygdala; expression; locus coeruleus; motivation; norepinephrine.

MeSH terms

  • Adrenergic beta-Antagonists / pharmacology
  • Analysis of Variance
  • Animals
  • Antipsychotic Agents / pharmacology
  • Avoidance Learning / drug effects
  • Avoidance Learning / physiology*
  • Central Amygdaloid Nucleus / drug effects
  • Central Amygdaloid Nucleus / metabolism*
  • Clozapine / analogs & derivatives
  • Clozapine / pharmacology
  • Conditioning, Classical / drug effects
  • Conditioning, Classical / physiology*
  • Dopamine beta-Hydroxylase / metabolism
  • Locus Coeruleus / physiology
  • Luminescent Proteins / genetics
  • Luminescent Proteins / metabolism
  • Male
  • Norepinephrine / metabolism*
  • Propranolol / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / metabolism
  • Red Fluorescent Protein
  • Transduction, Genetic
  • Transfer, Psychology / drug effects
  • Transfer, Psychology / physiology*


  • Adrenergic beta-Antagonists
  • Antipsychotic Agents
  • Luminescent Proteins
  • Receptors, G-Protein-Coupled
  • Propranolol
  • Dopamine beta-Hydroxylase
  • Clozapine
  • clozapine N-oxide
  • Norepinephrine