Acute and chronic dopamine receptor stimulation modulates AMPA receptor trafficking in nucleus accumbens neurons cocultured with prefrontal cortex neurons.

The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
Xiu SunMarina E Wolf

Abstract

Postsynaptic interactions between dopamine (DA) and glutamate receptors in the nucleus accumbens (NAc) are critical for addiction. To determine the effect of acute and repeated DA receptor stimulation on AMPA receptor (AMPAR) synaptic targeting in medium spiny NAc neurons, we developed a model system consisting of rat NAc neurons cocultured with prefrontal cortex neurons from enhanced green fluorescent protein-expressing mice. Cortical neurons restore excitatory input onto NAc neurons but are distinguishable based on fluorescence. First, we showed that brief D1-like agonist exposure increased AMPAR insertion onto extrasynaptic regions of NAc neuronal processes through a mechanism requiring protein kinase A. This facilitated the Ca2+/calmodulin dependent protein kinase II (CaMKII)-dependent synaptic incorporation of AMPARs in response to subsequent NMDA receptor (NMDAR) stimulation. Through this mechanism, DA may promote reward- and drug-related plasticity in the NAc. Then, to model effects of repeated in vivo cocaine exposure, we treated cocultures with DA (1 microm, 30 min) on days 7, 9, and 11 in culture. On day 15, NAc neurons exhibited increased synaptic AMPAR levels. This was associated with CaMKII activation and was block...Continue Reading

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