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

作者：Schumann Johanna; Matzner Henry; Michaeli Avner; Yaka Rami^*

来源：Neuroscience Letters, 2009, 461(2): 159-162.

DOI：10.1016/j.neulet.2009.06.002

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

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 (VIA) 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 VIA 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.

• 出版日期2009-9-11