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The Journal of Neuroscience, October 21, 2009, 29(42):13344-13352; doi:10.1523/JNEUROSCI.3546-09.2009

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Cellular/Molecular
The Time Course of Dopamine Transmission in the Ventral Tegmental Area

Christopher P. Ford,1 Paul E. M. Phillips,2,3 and John T. Williams1

1Vollum Institute, Oregon Health & Science University, Portland, Oregon 97239, and 2Departments of Psychiatry and Behavioral Sciences and 3Pharmacology, University of Washington, Seattle, Washington 98195

Correspondence should be addressed to John T. Williams, Vollum Institute, Oregon Health & Science University L474, 3181 SW Sam Jackson Park Road, Portland, OR 97239. Email: williamj{at}ohsu.edu

Synaptic transmission mediated by G-protein coupled receptors (GPCR) is not generally thought to be point-to-point. To determine the extent over which dopamine signals in the midbrain, the present study examined the concentration and time course of dopamine that underlies a D2-receptor IPSC (D2-IPSC) in the ventral tegmental area. Extracellular dopamine was measured electrochemically while simultaneously recording D2-IPSCs. The presence of dopamine was brief relative to the IPSC, suggesting that G-protein dependent potassium channel activation determined the IPSC time course. The activation kinetics of D2 receptor-dependent potassium current was studied using outside-out patch recordings with rapid application of dopamine. Dopamine applied at a minimum concentration of 10 µM for a maximum of 100 ms mimicked the IPSC. Higher concentrations applied for as little as 5 ms did not change the kinetics of the current. The results indicate that both the intrinsic kinetics of G-protein coupled receptor signaling and a rapidly rising high concentration of dopamine determine the time course of the IPSC. Thus, dopamine transmission in the midbrain is more localized then previously proposed.

Received July 22, 2009; revised Sept. 17, 2009; accepted Sept. 18, 2009.

Correspondence should be addressed to John T. Williams, Vollum Institute, Oregon Health & Science University L474, 3181 SW Sam Jackson Park Road, Portland, OR 97239. Email: williamj{at}ohsu.edu
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