Decreased dopamine D4 receptor expression increases extracellular glutamate and alters its regulation in mouse striatum.

作者: Theresa Currier Thomas , David K Grandy , Greg A Gerhardt , Paul EA Glaser

DOI: 10.1038/NPP.2008.74

关键词:

摘要: To better understand the effect of dopamine D4 receptor (DRD4) on glutamate (Glu) neurotransmission in brain, we utilized transgenic mice with partial or complete removal functional DRD4 plasma membrane expression (DRD4+/− and DRD4−/−, respectively). We measured resting extracellular Glu levels, clearance kinetics, KCl-evoked release striatum nucleus accumbens core these using vivo amperometry coupled to a novel microelectrode array configured for sub-second detection Glu. Recordings from DRD4−/− DRD4+/− were compared their wild-type littermates (DRD4+/+). Resting levels increased (p<0.01). kinetics significantly decreased dorsal (p<0.05). overflow was reliably but unchanged three groups. By contrast, no changes Glu, uptake observed among genotypes. These data indicate that is involved modulation neurotransmission, primarily striatum. A understanding control by may improve our physiological role disorders such as attention-deficit/hyperactivity disorder schizophrenia.

参考文章(62)
María Alejandra Berger, María Cristina Defagot, Marcelo J. Villar, Marta C. Antonelli, D4 dopamine and metabotropic glutamate receptors in cerebral cortex and striatum in rat brain. Neurochemical Research. ,vol. 26, pp. 345- 352 ,(2001) , 10.1023/A:1010990812840
George Paxinos, Keith B. J. Franklin, The Mouse Brain in Stereotaxic Coordinates ,(2007)
Martin H. Teicher, Carl M. Anderson, Ann Polcari, Carol A. Glod, Luis C. Maas, Perry F. Renshaw, Functional deficits in basal ganglia of children with attention-deficit/hyperactivity disorder shown with functional magnetic resonance imaging relaxometry. Nature Medicine. ,vol. 6, pp. 470- 473 ,(2000) , 10.1038/74737
Erin C Rutherford, Francois Pomerleau, Peter Huettl, Ingrid Strömberg, Greg A Gerhardt, None, Chronic second-by-second measures of l-glutamate in the central nervous system of freely moving rats Journal of Neurochemistry. ,vol. 102, pp. 712- 722 ,(2007) , 10.1111/J.1471-4159.2007.04596.X
Meleik A. Hebert, Greg A. Gerhardt, Age-Related Changes in the Capacity, Rate, and Modulation of Dopamine Uptake within the Striatum and Nucleus Accumbens of Fischer 344 Rats: An In Vivo Electrochemical Study Journal of Pharmacology and Experimental Therapeutics. ,vol. 288, pp. 879- 887 ,(1999)
G. Gerhardt, G. Rose, G. Jonsson, L. Olson, I. Stromberg, Gary A. Conboy, B. Hoffer, Dopaminergic neurotoxicity of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in the mouse: an in vivo electrochemical study. Journal of Pharmacology and Experimental Therapeutics. ,vol. 235, pp. 259- 265 ,(1985)
Greg A. Gerhardt, Michael R. Palmer, Characterization of the techniques of pressure ejection and microiontophoresis using in vivo electrochemistry. Journal of Neuroscience Methods. ,vol. 22, pp. 147- 159 ,(1987) , 10.1016/0165-0270(87)90009-4
Robert T Kennedy, Jonathan E Thompson, Thomas W Vickroy, In vivo monitoring of amino acids by direct sampling of brain extracellular fluid at ultralow flow rates and capillary electrophoresis. Journal of Neuroscience Methods. ,vol. 114, pp. 39- 49 ,(2002) , 10.1016/S0165-0270(01)00506-4
Marjorie A. Ariano, Eric R. Larson, Kurt L. Noblett, David R. Sibley, Michael S. Levine, Coexpression of striatal dopamine receptor subtypes and excitatory amino acid subunits. Synapse. ,vol. 26, pp. 400- 414 ,(1997) , 10.1002/(SICI)1098-2396(199708)26:4<400::AID-SYN8>3.0.CO;2-A