Fos-expressing neuronal ensemble in rat ventromedial prefrontal cortex encodes cocaine seeking but not food seeking in rats

Addict Biol. 2021 May;26(3):e12943. doi: 10.1111/adb.12943. Epub 2020 Jul 19.


Neuronal ensembles in ventromedial prefrontal cortex (vmPFC) play a role in both cocaine and palatable food seeking. However, it is unknown whether similar or different vmPFC neuronal ensembles mediate food and cocaine seeking. Here, we used the Daun02 inactivation procedure to assess whether the neuronal ensembles mediating food and cocaine seeking can be functionally distinguished. We trained male and female Fos-LacZ rats to self-administer palatable food pellets and cocaine on alternating days for 18 days. We then exposed the rats to a brief nonreinforced food- or cocaine-seeking test to induce Fos and β-gal in neuronal ensembles associated with food or cocaine seeking, respectively and infused Daun02 into vmPFC to ablate the β-gal-expressing ensembles. Two days later, we tested the rats for food or cocaine seeking under extinction conditions. Although inactivation of the food-seeking ensemble did not influence food or cocaine seeking, inactivation of the cocaine-seeking ensemble reduced cocaine seeking but not food seeking. Results indicate that the neuronal ensemble activated by cocaine seeking in vmPFC is functionally separate from the ensemble activated by food seeking.

Keywords: Daun02 inactivation; addiction; operant conditioning; vmPFC.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cocaine / administration & dosage*
  • Conditioning, Operant / drug effects
  • Conditioning, Operant / physiology
  • Drug-Seeking Behavior / drug effects
  • Drug-Seeking Behavior / physiology*
  • Extinction, Psychological / drug effects
  • Extinction, Psychological / physiology*
  • Female
  • Male
  • Neurons / drug effects
  • Neurons / metabolism*
  • Oncogene Proteins v-fos / metabolism*
  • Prefrontal Cortex / drug effects
  • Prefrontal Cortex / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Rats, Transgenic
  • Self Administration
  • Time Factors


  • Oncogene Proteins v-fos
  • Cocaine