NR2A/B-containing NMDA receptors mediate cocaine-induced synaptic plasticity in the VTA and cocaine psychomotor sensitization

Johanna Schumann, Henry Matzner, Avner Michaeli, Rami Yaka*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

21 Scopus citations


Cocaine-induced modifications of glutamatergic synaptic transmission in the mesolimbic system play a key role in adaptations that promote addictive behaviors. In particular, the activation of ionotropic glutamate N-methyl-d-aspartate receptor (NMDAR) in the ventral tegmental area (VTA) is critical for both cocaine-induced synaptic plasticity induced by a single cocaine injection and for the initiation of cocaine psychomotor sensitization. In this study, we set to determine whether the NR2 subunits of the NMDAR play a specific role in triggering cocaine-induced alterations in synaptic plasticity and the development of psychomotor sensitization. We found that inhibition of NR2A-containing NMDARs by NVP-AAM077, or NR2B-containing receptors by ifenprodil, blocked cocaine-induced increase in the AMPAR/NMDAR currents ratio, a measure of long-term potentiation (LTP) in vivo, in VTA neurons 24 h following a single cocaine injection. Furthermore, inhibition of the NR2A subunit during the development of psychomotor sensitization attenuated the enhanced locomotor activity following repeated cocaine injections. Together, these results suggest that NR2-containing NMDA receptors play an important role in the machinery that triggers synaptic and behavioral adaptations to drugs of abuse such as cocaine.

Original languageAmerican English
Pages (from-to)159-162
Number of pages4
JournalNeuroscience Letters
Issue number2
StatePublished - 11 Sep 2009

Bibliographical note

Funding Information:
We thank Dr. Y. Auberson of the Novartis Institutes for Biomedical Research (Basel, Switzerland) for the generous gift of NVP-AAM077. This research was supported by the Israel Science Foundation (grant no. 292/05 R.Y.). R. Yaka is affiliated with the David R. Bloom Center for Pharmacy and the Brettler Center for research in molecular pharmacology and therapeutics, School of Pharmacy, The Hebrew University of Jerusalem.


  • Cocaine
  • Ifenprodil
  • NMDA receptor
  • NVP-AAM077
  • Sensitization
  • Synaptic plasticity
  • VTA


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