Alterations in reward, fear and safety cue discrimination after inactivation of the rat prelimbic and infralimbic cortices

Neuropsychopharmacology. 2014 Sep;39(10):2405-13. doi: 10.1038/npp.2014.89. Epub 2014 Apr 14.


Accurate discrimination of environmental cues predicting reward, fear, or safety is important for survival. The prelimbic and infralimbic cortices are implicated in regulating reward-seeking and fear behaviors; however, no studies have examined their roles in discriminating among reward, fear, and safety cues. Using a discriminative conditioning task that includes presentations of a reward cue (paired with a reward pellet), fear cue (paired with footshock), and a compound fear+safety cue (no footshock) within the same sessions allowed us to assess the flexibility and precision of fear and reward-seeking behaviors to these cues. We found that fear behavior was appropriately limited to the fear cue in untreated rats, but during infralimbic cortical inactivation, similar levels of fear were seen to the fear and compound fear+safety cues. Reward-seeking behavior was also appropriately limited to the reward cue in untreated rats. Inactivating the prelimbic cortex altered discriminative reward seeking as rats with prelimbic inactivation did not increase their reward seeking behavior during the reward cue to the same degree as saline controls. Our results imply dissociable roles of the two cortical regions: the prelimbic cortex in precise discriminative reward seeking and the infralimbic cortex in discriminating between fear and safety cues. These data suggest that alterations in the balance of activity between areas homologous to the prelimbic and infralimbic cortices may be involved in the processes that go awry in anxiety and addiction disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Baclofen / pharmacology
  • Conditioning, Psychological / physiology
  • Cues
  • Discrimination, Psychological / physiology*
  • Electroshock
  • Extinction, Psychological / physiology
  • Fear / physiology*
  • Food
  • GABA-A Receptor Agonists / pharmacology
  • GABA-B Receptor Agonists / pharmacology
  • Male
  • Mental Recall / physiology
  • Muscimol / pharmacology
  • Prefrontal Cortex / drug effects
  • Prefrontal Cortex / physiology*
  • Rats, Long-Evans
  • Reward*


  • GABA-A Receptor Agonists
  • GABA-B Receptor Agonists
  • Muscimol
  • Baclofen