Enhancement of extinction learning attenuates ethanol-seeking behavior and alters plasticity in the prefrontal cortex

Justin T. Gass, Heather Trantham-Davidson, Amanda S. Kassab, William B. Glen, Michael Olive, L. Judson Chandler

Research output: Contribution to journalArticlepeer-review

60 Scopus citations


Addiction is a chronic relapsing disorder in which relapse is often initiated by exposure to drug-related cues. The present study examined the effects of mGluR5 activation on extinction of ethanol-cue-maintained responding, relapse-like behavior, and neuronal plasticity. Rats were trained to self-administer ethanol and then exposed to extinction training during which they were administered either vehicle or the mGluR5 positive allosteric modulator 3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl) or CDPPB. CDPPB treatment reduced active lever responding during extinction, decreased the total number of extinction sessions required to meet criteria, and attenuated cue-induced reinstatement of ethanol seeking. CDPPB facilitation of extinction was blocked by the local infusion of the mGluR5 antagonist 3-((2-methyl-4-thiazolyl)ethynyl) pyridine into the infralimbic (IfL) cortex, but had no effect when infused into the prelimbic (PrL) cortex. Analysis of dendritic spines revealed alterations in structural plasticity, whereas electrophysiological recordings demonstrated differential alterations in glutamatergic neurotransmission in the PrL and IfLcortex. Extinction was associated with increased amplitude of evoked synaptic PrL and IfLNMDA currents but reduced amplitude of PrL AMPA currents. Treatment with CDPPB prevented the extinction-induced enhancement of NMDA currents in PrL without affecting NMDA currents in the IfL. Whereas CDPPB treatment did not alter the amplitude of PrL or IfLAMPA currents, it did promote the expression of IfLcalcium-permeable GluR2-lacking receptors in both abstinence- and extinction-trained rats, but had no effect in ethanol-naive rats. These results confirm changes in the PrL and IfLcortex in glutamatergic neurotransmission during extinction learning and demonstrate that manipulation of mGluR5 facilitates extinction of ethanol cues in association with neuronal plasticity.

Original languageEnglish (US)
Pages (from-to)7562-7574
Number of pages13
JournalJournal of Neuroscience
Issue number22
StatePublished - 2014


  • Alcohol
  • Extinction
  • Glutamate
  • MTEP
  • Mglur5
  • Plasticity

ASJC Scopus subject areas

  • Neuroscience(all)


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