TY - JOUR T1 - Dopamine Receptor Stimulation Modulates AMPA Receptor Synaptic Insertion in Prefrontal Cortex Neurons JF - The Journal of Neuroscience JO - J. Neurosci. SP - 7342 LP - 7351 DO - 10.1523/JNEUROSCI.4603-04.2005 VL - 25 IS - 32 AU - Xiu Sun AU - Yun Zhao AU - Marina E. Wolf Y1 - 2005/08/10 UR - http://www.jneurosci.org/content/25/32/7342.abstract N2 - 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. ER -