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- Title
Cooperative Activation of Dopamine D[sub1] and D[sub2] Receptors Increases Spike Firing of Nucleus Accumbens Neurons via G-Protein Βγ Subunits.
- Authors
Hopf, F. Woodward; Cascini, Maria Grazia; Gordon, Adrienne S.; Diamond, Ivan; Bonci, Antonello
- Abstract
Dopamine in the nucleus accumbens modulates both motivational and addictive behaviors. Dopamine D[sub1] and D[sub2] receptors are generally considered to exert opposite effects at the cellular level, but many behavioral studies find an apparent cooperative effect of D[sub1] and D[sub2] 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 D[sub1] and D[sub2] receptors. One intracellular mechanism that might underlie cooperativity of D[sub1] and D[sub2] receptors is activation of specific subtypes of adenylyl cyclases by G-protein βγ subunits (G[subβγ]) released from the G[subi/o]-linked D[sub2] receptor in combination with G[subαs]-like subunits from the D[sub1] receptor. In this regard, dopaminergic enhancement of spike firing was prevented by inhibitors of protein kinase A or G[subβγ]. Furthermore, intracellular perfusion with G[subβγ] enabled D[sub1] receptor activation but not D[sub2] 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 D[sub1] and D[sub2] receptors in the nucleus accumbens could mediate dopamine-dependent behaviors.
- Subjects
DOPAMINE receptors; DOPAMINERGIC neurons; NUCLEUS accumbens; NEUROBEHAVIORAL disorders; G proteins; POTASSIUM channels
- Publication
Journal of Neuroscience, 2003, Vol 23, Issue 12, p5079
- ISSN
0270-6474
- Publication type
Article
- DOI
10.1523/JNEUROSCI.23-12-05079.2003