Facilitated extinction of morphine conditioned place preference with Tat-GluA2(3Y) interference peptide

Behav Brain Res. 2012 Aug 1;233(2):389-97. doi: 10.1016/j.bbr.2012.05.026. Epub 2012 May 23.


Neuroplasticity including long-term depression (LTD) has been implicated in both learning processes and addiction. LTD can be blocked by intravenous administration of the interference peptide Tat-GluA2(3Y) that prevents regulated endocytosis of the alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA) receptor. In this study, Tat-GluA2(3Y) was used to assess the role of LTD in the induction, expression, extinction and reinstatement of morphine-induced conditioned place preference (CPP). CPP was established in rats by pairing morphine (5 mg/kg, i.p.) or saline with a specific environmental context using a balanced protocol. Tat-GluA2(3Y) (0; 1.5; 2.25 nmol/g; i.v.), scrambled peptide (Tat-GluA2(Sc)), or vehicle was administered during the acquisition phase or prior to the test for CPP. Tat-GluA2(3Y) had no effect on the induction or initial expression of morphine-induced CPP. Rats that received Tat-GluA2(3Y) or Tat-GluA2(Sc) during acquisition were subsequently tested for 11 consecutive days in order to extinguish morphine CPP. CPP was then reinstated by an injection of morphine (5 mg/kg, i.p.). Co-administration of morphine and Tat-GluA2(3Y) during acquisition greatly facilitated extinction of CPP without affecting morphine-induced reinstatement of CPP. Using an intermittent retest schedule with bi-weekly tests to measure the maintenance of CPP, Tat-GluA2(3Y) during the acquisition phase had no effect on the maintenance of CPP. We propose that co-administration of Tat-GluA2(3Y) with morphine during acquisition of CPP weakens the association between morphine and contextual cues leading to rapid extinction of morphine CPP with repeated daily testing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Behavior, Animal
  • Conditioning, Operant / drug effects*
  • Dose-Response Relationship, Drug
  • Extinction, Psychological / drug effects*
  • Food
  • Male
  • Morphine / pharmacology*
  • Motivation / drug effects
  • Narcotics / pharmacology*
  • Peptides / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, AMPA / chemistry*
  • Reinforcement, Psychology


  • Narcotics
  • Peptides
  • Receptors, AMPA
  • Morphine
  • glutamate receptor ionotropic, AMPA 2