Distinct Subpopulations of Nucleus Accumbens Dynorphin Neurons Drive Aversion and Reward

Neuron. 2015 Sep 2;87(5):1063-77. doi: 10.1016/j.neuron.2015.08.019.


The nucleus accumbens (NAc) and the dynorphinergic system are widely implicated in motivated behaviors. Prior studies have shown that activation of the dynorphin-kappa opioid receptor (KOR) system leads to aversive, dysphoria-like behavior. However, the endogenous sources of dynorphin in these circuits remain unknown. We investigated whether dynorphinergic neuronal firing in the NAc is sufficient to induce aversive behaviors. We found that photostimulation of dynorphinergic cells in the ventral NAc shell elicits robust conditioned and real-time aversive behavior via KOR activation, and in contrast, photostimulation of dorsal NAc shell dynorphin cells induced a KOR-mediated place preference and was positively reinforcing. These results show previously unknown discrete subregions of dynorphin-containing cells in the NAc shell that selectively drive opposing behaviors. Understanding the discrete regional specificity by which NAc dynorphinerigic cells regulate preference and aversion provides insight into motivated behaviors that are dysregulated in stress, reward, and psychiatric disease.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Action Potentials / genetics
  • Animals
  • Avoidance Learning / physiology*
  • Conditioning, Operant
  • Dynorphins / genetics
  • Dynorphins / metabolism*
  • Electric Stimulation
  • Gene Expression Regulation
  • In Vitro Techniques
  • Luminescent Proteins / genetics
  • Luminescent Proteins / metabolism
  • Male
  • Maze Learning
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neurons / classification
  • Neurons / physiology*
  • Nucleus Accumbens / cytology*
  • Photic Stimulation
  • Protein Precursors / genetics
  • Protein Precursors / metabolism*
  • Receptors, Dopamine D2 / genetics
  • Receptors, Dopamine D2 / metabolism
  • Reward*
  • Self Stimulation
  • Time Factors
  • Wireless Technology


  • DRD2 protein, mouse
  • Luminescent Proteins
  • Protein Precursors
  • Receptors, Dopamine D2
  • pre-prodynorphin
  • Dynorphins