Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
22
pubmed:dateCreated
2004-6-3
pubmed:abstractText
Although the importance of dopamine (DA) for prefrontal cortical (PFC) cognitive functions is widely recognized, the nature of DA actions in the PFC remains controversial. A critical component in DA actions is its modulation of glutamate transmission, which can be different when specific receptors are activated. To obtain a clear picture of cellular mechanisms involved in these interactions, we studied the effects of DA-glutamate coactivation on pyramidal cell excitability in brain slices obtained from developmentally mature rats using whole-cell patch-clamp recordings. Bath application of NMDA, AMPA, and the D1 agonist SKF38393 induced concentration-dependent excitability increases, whereas bath application of the D2 receptor agonist quinpirole induced a concentration-dependent excitability decrease. The NMDA-mediated response was potentiated by SKF38393. This NMDA-D1 synergism required postsynaptic intracellular Ca2+ and protein kinase A (PKA) and was independent of membrane depolarization. On the other hand, the excitatory effects of both NMDA and AMPA were attenuated by a D2 agonist. Surprisingly, the D2-NMDA interaction was also blocked by the GABA(A) antagonists bicuculline and picrotoxin, suggesting that the inhibitory action of D2 receptors on NMDA-induced responses in the PFC may be mediated by GABAergic interneurons. In contrast, the D2-AMPA interaction involves inhibition of PKA and activation of phospholipase lipase C-IP3 and intracellular Ca2+ at a postsynaptic level. Thus, the modulatory actions of D1 and D2 receptors on PFC pyramidal cell excitability are mediated by multiple intracellular mechanisms and by activation of GABA(A) receptors, depending on the glutamate receptor subtypes involved.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Calcium, http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP-Dependent Protein Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Dopamine Agonists, http://linkedlifedata.com/resource/pubmed/chemical/Dopamine Antagonists, http://linkedlifedata.com/resource/pubmed/chemical/Excitatory Amino Acid Agonists, http://linkedlifedata.com/resource/pubmed/chemical/GABA Antagonists, http://linkedlifedata.com/resource/pubmed/chemical/Glutamic Acid, http://linkedlifedata.com/resource/pubmed/chemical/N-Methylaspartate, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Dopamine D1, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Dopamine D2, http://linkedlifedata.com/resource/pubmed/chemical/alpha-Amino-3-hydroxy-5-methyl-4-iso...
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1529-2401
pubmed:author
pubmed:issnType
Electronic
pubmed:day
2
pubmed:volume
24
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5131-9
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:15175382-Action Potentials, pubmed-meshheading:15175382-Animals, pubmed-meshheading:15175382-Calcium, pubmed-meshheading:15175382-Cyclic AMP-Dependent Protein Kinases, pubmed-meshheading:15175382-Dopamine, pubmed-meshheading:15175382-Dopamine Agonists, pubmed-meshheading:15175382-Dopamine Antagonists, pubmed-meshheading:15175382-Dose-Response Relationship, Drug, pubmed-meshheading:15175382-Drug Synergism, pubmed-meshheading:15175382-Excitatory Amino Acid Agonists, pubmed-meshheading:15175382-GABA Antagonists, pubmed-meshheading:15175382-Glutamic Acid, pubmed-meshheading:15175382-Male, pubmed-meshheading:15175382-N-Methylaspartate, pubmed-meshheading:15175382-Patch-Clamp Techniques, pubmed-meshheading:15175382-Prefrontal Cortex, pubmed-meshheading:15175382-Pyramidal Cells, pubmed-meshheading:15175382-Rats, pubmed-meshheading:15175382-Rats, Sprague-Dawley, pubmed-meshheading:15175382-Reaction Time, pubmed-meshheading:15175382-Receptors, Dopamine D1, pubmed-meshheading:15175382-Receptors, Dopamine D2, pubmed-meshheading:15175382-Signal Transduction, pubmed-meshheading:15175382-alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
pubmed:year
2004
pubmed:articleTitle
Dopamine-glutamate interactions controlling prefrontal cortical pyramidal cell excitability involve multiple signaling mechanisms.
pubmed:affiliation
Center for Neuropharmacology and Neuroscience, Albany Medical College, Albany, New York 12208, USA. tsengky@mail.amc.edu
pubmed:publicationType
Journal Article, In Vitro, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't