Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2003-6-30
pubmed:abstractText
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 betagamma subunits (Gbetagamma) released from the Gi/o-linked D2 receptor in combination with Galpha(s)-like subunits from the D1 receptor. In this regard, dopaminergic enhancement of spike firing was prevented by inhibitors of protein kinase A or Gbetagamma. Furthermore, intracellular perfusion with Gbetagamma 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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1529-2401
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
23
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5079-87
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:12832531-Action Potentials, pubmed-meshheading:12832531-Animals, pubmed-meshheading:12832531-Cyclic AMP, pubmed-meshheading:12832531-Cyclic AMP-Dependent Protein Kinases, pubmed-meshheading:12832531-Dopamine, pubmed-meshheading:12832531-Dopamine Agonists, pubmed-meshheading:12832531-Dopamine Antagonists, pubmed-meshheading:12832531-GTP-Binding Proteins, pubmed-meshheading:12832531-Male, pubmed-meshheading:12832531-Neurons, pubmed-meshheading:12832531-Nucleus Accumbens, pubmed-meshheading:12832531-Patch-Clamp Techniques, pubmed-meshheading:12832531-Potassium Channels, pubmed-meshheading:12832531-Protein Subunits, pubmed-meshheading:12832531-Rats, pubmed-meshheading:12832531-Rats, Sprague-Dawley, pubmed-meshheading:12832531-Reaction Time, pubmed-meshheading:12832531-Receptors, Dopamine D1, pubmed-meshheading:12832531-Receptors, Dopamine D2
pubmed:year
2003
pubmed:articleTitle
Cooperative activation of dopamine D1 and D2 receptors increases spike firing of nucleus accumbens neurons via G-protein betagamma subunits.
pubmed:affiliation
Ernest Gallo Clinic and Research Center, Department of Neurology, University of California, San Francisco, Emeryville, California 94608, USA.
pubmed:publicationType
Journal Article, In Vitro, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't