TY - JOUR
T1 - D1 dopamine receptor stimulation increases the rate of AMPA receptor insertion onto the surface of cultured nucleus accumbens neurons through a pathway dependent on protein kinase A
AU - Mangiavacchi, Simona
AU - Wolf, Marina E.
PY - 2004/3
Y1 - 2004/3
N2 - Trafficking of α-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptors is an important determinant of synaptic strength. Our prior work suggests that D1 dopamine (DA) receptors regulate AMPA receptor trafficking. This is a possible mechanism by which amphetamine and cocaine, which indirectly stimulate D1 receptors, may alter synaptic strength in addiction- related neuronal circuits. Post-natal rat nucleus accumbens (NAc) cultures were used to study the role of protein kinase A (PKA) in D1 receptor regulation of the surface expression of the AMPA receptor subunit GluR1. Using an immunocytochemical assay that selectively detects newly externalized GluR1, we found that the rate of GluR1 externalization is enhanced by the D1 agonist SKF 81297 (100 nM-1 μm). This was blocked by a D1 receptor antagonist (SCH 23390; 10 μM) and by two different cell-permeable PKA inhibitors, KT5720 (2 and 10 μM) and RpcAMPS (10 μM). Conversely, the PKA activator SpcAMPS increased the rate of GluR1 externalization in a concentration-dependent manner. A maximally effective concentration of SpcAMPS (10 μM) occluded the effect of SKF 81297 (1 μM) on GluR1 externalization. Using similar cultures, we showed previously that D1 receptor stimulation increases GluR1 phosphorylation at the PKA site. Together, our findings suggest that PKA phosphorylation of GluR1 is required for GluR1 externalization in response to D1 receptor stimulation.
AB - Trafficking of α-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptors is an important determinant of synaptic strength. Our prior work suggests that D1 dopamine (DA) receptors regulate AMPA receptor trafficking. This is a possible mechanism by which amphetamine and cocaine, which indirectly stimulate D1 receptors, may alter synaptic strength in addiction- related neuronal circuits. Post-natal rat nucleus accumbens (NAc) cultures were used to study the role of protein kinase A (PKA) in D1 receptor regulation of the surface expression of the AMPA receptor subunit GluR1. Using an immunocytochemical assay that selectively detects newly externalized GluR1, we found that the rate of GluR1 externalization is enhanced by the D1 agonist SKF 81297 (100 nM-1 μm). This was blocked by a D1 receptor antagonist (SCH 23390; 10 μM) and by two different cell-permeable PKA inhibitors, KT5720 (2 and 10 μM) and RpcAMPS (10 μM). Conversely, the PKA activator SpcAMPS increased the rate of GluR1 externalization in a concentration-dependent manner. A maximally effective concentration of SpcAMPS (10 μM) occluded the effect of SKF 81297 (1 μM) on GluR1 externalization. Using similar cultures, we showed previously that D1 receptor stimulation increases GluR1 phosphorylation at the PKA site. Together, our findings suggest that PKA phosphorylation of GluR1 is required for GluR1 externalization in response to D1 receptor stimulation.
KW - AMPA receptors
KW - D1 dopamine receptors
KW - GluR1
KW - Nucleus accumbens
KW - Protein kinase A
KW - Receptor trafficking
UR - http://www.scopus.com/inward/record.url?scp=1442323982&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=1442323982&partnerID=8YFLogxK
U2 - 10.1046/j.1471-4159.2003.02248.x
DO - 10.1046/j.1471-4159.2003.02248.x
M3 - Article
C2 - 15009682
AN - SCOPUS:1442323982
SN - 0022-3042
VL - 88
SP - 1261
EP - 1271
JO - Journal of neurochemistry
JF - Journal of neurochemistry
IS - 5
ER -