The role of medial prefrontal cortex in extinction and reinstatement of alcohol-seeking in rats

Eur J Neurosci. 2013 Jan;37(2):259-68. doi: 10.1111/ejn.12031. Epub 2012 Oct 29.


The prelimbic (PL) and infralimbic (IL) medial prefrontal cortex (mPFC) are thought to play opposing roles in drug-seeking behaviour. Specifically, the PL promotes drug-seeking whereas the IL is necessary for the inhibition of drug-seeking during extinction. We studied the roles of the PL, IL and dorsal peduncular PFC (DP) in the expression of context-induced reinstatement, reacquisition and extinction of alcoholic beer-seeking. In context-induced reinstatement (renewal), animals were trained to nosepoke for alcoholic beer (context A), extinguished (context B) and then tested in context A and B. In reacquisition, animals received the same instrumental training and extinction without any contextual manipulation. On test, alcoholic beer was again available and responding was compared with naive controls. Just prior to the test, rats received bilateral infusion of baclofen/muscimol into the PL, IL or DP. Reversible inactivation of the PL attenuated ABA renewal but augmented reacquisition. Reversible inactivation of IL had no effect on the reinstatement or reacquisition of alcoholic beer-seeking and had no effect on extinction expression (ABB and AAA). IL inactivation did, however, increase the latencies with which animals responded on test but only when animals were tested in the extinction context. DP inactivation had no effect on reinstatement or reacquisition. These studies are inconsistent with the view that PL and IL exert opposing effects on drug-seeking. Rather, they support the view that PL is important for retrieval of drug-seeking contingency information and that the use of contextual information is enhanced with IL manipulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Baclofen / pharmacology
  • Beer
  • Drug-Seeking Behavior / drug effects
  • Drug-Seeking Behavior / physiology*
  • Ethanol / toxicity*
  • Extinction, Psychological / drug effects
  • Extinction, Psychological / physiology
  • GABA-A Receptor Agonists / pharmacology
  • GABA-B Receptor Agonists / pharmacology
  • Male
  • Muscimol / pharmacology
  • Prefrontal Cortex / drug effects
  • Prefrontal Cortex / physiology*
  • Rats
  • Rats, Long-Evans
  • Reaction Time


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