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The Journal of Neuroscience, June 15, 2003, 23(12):5079-5087
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Cooperative Activation of Dopamine D1 and D2 Receptors Increases Spike Firing of Nucleus Accumbens Neurons via G-Protein   Subunits
F. Woodward Hopf,1,2
Maria Grazia Cascini,1
Adrienne S. Gordon,1
Ivan Diamond,1 and
Antonello Bonci1,2
1Ernest Gallo Clinic and Research Center, Department of Neurology, and 2Wheeler Center for the Neurobiology of Addiction, University of California, San Francisco, Emeryville, California 94608
Dopamine in the nucleus accumbens modulates both motivational and addictive behaviors. Dopamine D1 and D2 receptors are generally considered to exert opposite effects at the cellular level, but many behavioral studies find an apparent cooperative effect of D1 and D2 receptors in the nucleus accumbens. Here, we show that a dopamine-induced enhancement of spike firing in nucleus accumbens neurons in brain slices required both D1 and D2 receptors. One intracellular mechanism that might underlie cooperativity of D1 and D2 receptors is activation of specific subtypes of adenylyl cyclases by G-protein   subunits (G) released from the Gi/o-linked D2 receptor in combination with G s-like subunits from the D1 receptor. In this regard, dopaminergic enhancement of spike firing was prevented by inhibitors of protein kinase A or G. Furthermore, intracellular perfusion with G enabled D1 receptor activation but not D2 receptor activation to enhance spike firing. Finally, our data suggest that these pathways may increase spike firing by inhibition of a slow A-type potassium current. These results provide evidence for a novel cellular mechanism through which cooperative action of D1 and D2 receptors in the nucleus accumbens could mediate dopamine-dependent behaviors.
Key words: nucleus accumbens; dopamine; G-protein subunits; PKA; K+ channels; spike firing
Received Jan. 16, 2003;
revised Apr. 4, 2003;
accepted Apr. 7, 2003.
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