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- Title
Regional Differences in Extracellular Dopamine and Serotonin Assessed by In Vivo Microdialysis in Mice Lacking Dopamine and/or Serotonin Transporters.
- Authors
Hao-wei Shen; Hagino, Yoko; Kobayashi, Hideaki; Shinohara-Tanaka, Keiko; Ikeda, Kazutaka; Yamamoto, Hideko; Yamamoto, Toshifumi; Lesch, Klaus-Peter; Murphy, Dennis L.; Hall, F. Scott; Uhl, George R.; Sora, Ichiro
- Abstract
Cocaine conditioned place preference (CPP) is intact in dopamine transporter (DAT) knockout (KO) mice and enhanced in serotonin transporter (SERT) KO mice. However, cocaine CPP is eliminated in double-KO mice with no DAT and either no or one SERT gene copy. To help determine mechanisms underlying these effects, we now report examination of baselines and drug-induced changes of extracellular dopamine (DAex) and serotonin (5-HTex) levels in microdialysates from nucleus accumbens (NAc), caudate putamen (CPu), and prefrontal cortex (PFc) of wild-type, homozygous DAT- or SERT-KO and heterozygous or homozygous DAT/S ERT double- KO mice, which are differentially rewarded by cocaine. Cocaine fails to increase DAex in NAc of DAT-KO mice. By contrast, systemic cocaine enhances DAex in both CPu and PFc of DAT-KO mice though local cocaine fails to affect DAex in CPu. Adding SERT to DAT deletion attenuates the cocaine-induced DAex increases found in CPu, but not those found in PFc. The selective SERT blocker fluoxetine increases DAex in CPu of DAT-KO mice, while cocaine and the selective DAT blocker GBR 12909 increase 5-HTex in CPu of SERT-KO mice. These data provide evidence that (a) cocaine increases DAex in PFc independently of DAT and that (b), in the absence of SERT, CPu levels of 5-HTex can be increased by blocking DAT. Cocaine-induced alterations in CPu DA levels in DAT-, SERT-, and DAT/SERT double-KO mice appear to provide better correlations with cocaine CPP than cocaine-induced DA level alterations in NAc or PFc. Neuro psychopharmacology (2004) 29, 1790-I 799, advance online publication, 30 june 2004; dol: 10.1 038/s.npp. 1300476
- Publication
Neuropsychopharmacology, 2004, Vol 29, Issue 10, p1790
- ISSN
0893-133X
- Publication type
Academic Journal
- DOI
10.1038/sj.npp.1300476