Preference for Cocaine is Represented in the Orbitofrontal Cortex by an Increased Proportion of Cocaine Use-Coding Neurons

Cereb Cortex. 2018 Mar 1;28(3):819-832. doi: 10.1093/cercor/bhw398.


Cocaine addiction is a harmful preference for drug use over and at the expense of other nondrug-related activities. Here we identify in the rat orbitofrontal cortex (OFC) a mechanism that explains individual preferences between cocaine use and an alternative, nondrug action. OFC neuronal activity was recorded while rats performed each of these 2 actions separately or while they chose between them. First, we found that these actions are encoded by 2 nonoverlapping neuronal populations and that the relative size of the cocaine population represented individual preferences. A larger relative size was only observed in cocaine-preferring individuals. Second, OFC neurons encoding a given individual's preferred action progressively fired more than other action-coding neurons few seconds before the preferred action was actually chosen, suggesting a prechoice neuronal competition for action selection. In cocaine-preferring rats, this manifested by a prechoice ramping-up activity in favor of the cocaine population. Finally, pharmacological manipulation of prechoice activity in favor of the cocaine population caused nondrug-preferring rats to shift their choice to cocaine. Overall, this study suggests that an individual preference for cocaine is represented in the OFC by a population size bias that systematically advantages cocaine use-coding neurons during prechoice competition for action selection.

Keywords: addiction; choice; cocaine; orbitofrontal cortex; preference.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects
  • Anesthetics, Local / administration & dosage*
  • Animals
  • Choice Behavior / drug effects
  • Choice Behavior / physiology
  • Cocaine / administration & dosage*
  • Conditioning, Operant / drug effects*
  • Male
  • Neurons / drug effects*
  • Neurons / physiology
  • Prefrontal Cortex / cytology*
  • Rats
  • Rats, Wistar
  • Reaction Time / drug effects
  • Reward
  • Saccharin / administration & dosage


  • Anesthetics, Local
  • Saccharin
  • Cocaine