Dopamine receptor stimulation modulates AMPA receptor synaptic insertion in prefrontal cortex neurons

Xiu Sun, Yun Zhao, Marina E. Wolf

Research output: Contribution to journalArticle

212 Scopus citations

Abstract

Addiction is believed to involve glutamate-dependent forms of synaptic plasticity that promote the formation of new habits focused on drug seeking. We used primary cultures of rat prefrontal cortex (PFC) neurons to explore mechanisms by which dopamine-releasing psychomotor stimulants such as cocaine and amphetamine influence synaptic plasticity, focusing on AMPA receptor trafficking because of its key role in long-term potentiation (LTP). Brief stimulation of D1 dopamine receptors increased surface expression of glutamate receptor 1 (GluR1)-containing AMPA receptors through a protein kinase A-dependent mechanism, by increasing their rate of externalization at extrasynaptic sites. Newly externalized GluR1 remained extrasynaptic under basal conditions but could be translocated into synapses by subsequent NMDA receptor activation. These results suggest that D1 receptors may facilitate LTP by increasing the AMPA receptor pool available for synaptic insertion. However, stimulation of D2 receptors decreased surface and synaptic GluR1 expression. These findings are discussed in the context of evidence that D1 and D2 receptors act independently rather than antagonistically in the intact PFC. D1 receptor facilitation of AMPA receptor synaptic insertion helps explain D1 receptor-dependent facilitation of LTP and learning in the normal brain. Abnormal engagement of this mechanism during unregulated dopamine release may account for maladaptive plasticity after repeated exposure to cocaine or amphetamine.

Original languageEnglish (US)
Pages (from-to)7342-7351
Number of pages10
JournalJournal of Neuroscience
Volume25
Issue number32
DOIs
StatePublished - Aug 10 2005

Keywords

  • AMPA receptor
  • Addiction
  • Dopamine
  • LTP
  • Plasticity
  • Protein kinase A

ASJC Scopus subject areas

  • Neuroscience(all)

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