Inactivation of the medial prefrontal cortex of the rat impairs strategy set-shifting, but not reversal learning, using a novel, automated procedure

Behav Brain Res. 2008 Jun 26;190(1):85-96. doi: 10.1016/j.bbr.2008.02.008. Epub 2008 Feb 15.


The medial prefrontal cortex (mPFC) of the rat plays an essential role in behavioral flexibility, as lesions or inactivations of this region impair shifting between strategies or attentional sets using a variety of different behavioral tests. In the present study, we assessed the effects of inactivation of the mPFC on strategy set-shifting and reversal learning, using a novel, automated procedure conducted in an operant chamber. In Experiment 1, inactivation of the mPFC with bupivacaine did not impair the initial learning of a visual-cue (i.e.; always press the lever with a cue light illuminated above it) or a response (i.e.; always press the left lever) discrimination. Control rats required greater number of trials to shift from using a visual-cue to a response strategy than the opposite shift. mPFC inactivation impaired performance of a visual-cue-response set-shift, but not the easier response-visual-cue shift. In Experiment 2, pre-exposure to the visual-cue stimulus lights increased the difficulty of the response-visual-cue shift, reflected by a greater number of trials required by control rats to achieve criterion relative to those in Experiment 1. Under these conditions, inactivation of the mPFC did impair performance of this set-shift. In contrast, mPFC inactivation did not affect reversal learning of a response discrimination. These findings highlight the utility of this automated procedure for assessing set-shifting mediated by the mPFC. Furthermore, they reveal that the relative difficulty of the type of shift rats are required to perform has a direct impact on whether or not the mPFC contributes to this form of behavioral flexibility.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anesthetics, Local / pharmacology
  • Animals
  • Attention Deficit Disorder with Hyperactivity / chemically induced
  • Attention Deficit Disorder with Hyperactivity / pathology
  • Attention Deficit Disorder with Hyperactivity / physiopathology*
  • Behavior, Animal / physiology
  • Bupivacaine / pharmacology
  • Conditioning, Operant / drug effects
  • Conditioning, Operant / physiology*
  • Cues
  • Discrimination, Psychological / drug effects
  • Discrimination, Psychological / physiology
  • Photic Stimulation
  • Prefrontal Cortex / drug effects
  • Prefrontal Cortex / physiology*
  • Rats
  • Rats, Long-Evans
  • Reversal Learning / drug effects
  • Reversal Learning / physiology*


  • Anesthetics, Local
  • Bupivacaine