Stability of surface NMDA receptors controls synaptic and behavioral adaptations to amphetamine (Nat Neurosci, 2009, 12:602-610)

報告日期: 2009/12/25
報告時間: 16:00/16:50
報告學生: 余泱蓉
講評老師: 游一龍

Stability of surface NMDA receptors controls synaptic and behavioral adaptation to amphetamine

Li-Min Mao, Wei Wang, Xiang-Ping Chu, Guo-Chi Zhang, Xian-Yu Liu, Yuan-Jian Yang,Michelle Haines, Christopher J Papasian, Eugene E Fibuch, Shilpa Buch, Jian-Guo Chen & John Q Wang

NATURE NEUROSCIENCE  12: 602-610, 2009


Speaker: 余泱蓉

Commentator:游一龍 老師

Date: 16:00~ 16:50, Dec 25, 2009

Place: Room 602



Drug addiction was thought to result from persistent molecular adaptions in response to repeated psychostimulant exposure, such as amphetamine (AMPH), and most attention has been given to the mesolimbic system. Recently, it is known that glutamatergic mechanisms also play a central role in processes underlying the development and maintenance of drug addiction. In glutamatergic neuron, NMDA receptor (NMDAR) is a major form of ionotropic receptor, and is associated with synaptic plasticity. Among NMDAR, NR2B subunit is known to be abundant in the striatum. In many forms of synaptic plasticity, functional NR2B play an important role in the pathogenesis of various neurological disorders and the physiology of striatal neurons, but the role of NR2B in AMPH-induced behavioral sensitization is remain unclear. Therefore, the authors want to address this issue in this study.

In this study, chronic exposure to the AMPH induced selective downregulation of NR2B subunits in the surface membrane of rat striatal neurons at synaptic sites. Repeated AMPH induced-NR2B downregulation result from destabilization of surface NR2B subunits caused by ubiquitination and degradation of NR2B-anchoring proteins. Furthermore, the downregulation of synaptic NR2B fail to induce long-term depression. Behaviorally, genetic disruption of NR2B or its antagonist induced behavioral sensitization, and restoration of NR2B loss prevented behavioral sensitization to AMPH. These results suggest the regulation and remodeling effect of NR2B in excitatory synapse and persistent psychomotor plasticity underling AMPH treatment.



Tzschentke, T.M.& Schmidt, W.J.  Glutamatergic mechanisms in addiction.      Mol. Psychiatry 8: 373–382, 2003.