D1 dopamine receptor stimulation increases GluR1 phosphorylation in postnatal nucleus accumbens cultures

Abstract

Postsynaptic interactions between dopamine and glutamate receptors in the nucleus accumbens are critical for acute responses to drugs of abuse and for neuroadaptations resulting from their chronic administration. We tested the hypothesis that D1 dopamine receptor stimulation increases phosphorylation of the AMPA receptor subunit GluR1 at the protein kinase A phosphorylation site (Ser845). Nucleus accumbens cell cultures were prepared from postnatal day 1 rats. After 14 days in culture, GluR1 phosphorylation was measured by western blotting using phosphorylation site-specific antibodies. The D1 receptor agonist SKF 81297 increased Ser845 phosphorylation in a concentration-dependent manner, with marked increases occurring within 5 min. This was prevented by the D1 receptor antagonist SCH 23390 and the protein kinase A inhibitor H89, and reproduced by forskolin. The D2 receptor agonist quinpirole attenuated the response to D1 receptor stimulation. Neither D1 nor D2 receptor agonists altered GluR1 phosphorylation at Ser831, the site phosphorylated by protein kinase C and calcium/calmodulin-dependent protein kinase II. In other systems, phosphorylation of GluR1 at Ser845 is associated with enhancement of AMPA receptor currents. Thus, the present results suggest that AMPA receptor transmission in the nucleus accumbens may be augmented by concurrent D1 receptor stimulation.