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Regional differences in extracellular dopamine and serotonin assessed by in vivo microdialysis in mice lacking dopamine and/or serotonin transporters.
Neuropsychopharmacology. 2004 Oct; 29(10):1790-9.N

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-HT(ex)) 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/SERT 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 GBR12909 increase 5-HT(ex) 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-HT(ex) 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.

Authors+Show Affiliations

Department of Molecular Psychiatry, Tokyo Institute of Psychiatry, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15226739

Citation

Shen, Hao-Wei, et al. "Regional Differences in Extracellular Dopamine and Serotonin Assessed By in Vivo Microdialysis in Mice Lacking Dopamine And/or Serotonin Transporters." Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology, vol. 29, no. 10, 2004, pp. 1790-9.
Shen HW, Hagino Y, Kobayashi H, et al. Regional differences in extracellular dopamine and serotonin assessed by in vivo microdialysis in mice lacking dopamine and/or serotonin transporters. Neuropsychopharmacology. 2004;29(10):1790-9.
Shen, H. W., Hagino, Y., Kobayashi, H., Shinohara-Tanaka, K., Ikeda, K., Yamamoto, H., Yamamoto, T., Lesch, K. P., Murphy, D. L., Hall, F. S., Uhl, G. R., & Sora, I. (2004). Regional differences in extracellular dopamine and serotonin assessed by in vivo microdialysis in mice lacking dopamine and/or serotonin transporters. Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology, 29(10), 1790-9.
Shen HW, et al. Regional Differences in Extracellular Dopamine and Serotonin Assessed By in Vivo Microdialysis in Mice Lacking Dopamine And/or Serotonin Transporters. Neuropsychopharmacology. 2004;29(10):1790-9. PubMed PMID: 15226739.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Regional differences in extracellular dopamine and serotonin assessed by in vivo microdialysis in mice lacking dopamine and/or serotonin transporters. AU - Shen,Hao-Wei, AU - Hagino,Yoko, AU - Kobayashi,Hideaki, AU - Shinohara-Tanaka,Keiko, AU - Ikeda,Kazutaka, AU - Yamamoto,Hideko, AU - Yamamoto,Toshifumi, AU - Lesch,Klaus-Peter, AU - Murphy,Dennis L, AU - Hall,F Scott, AU - Uhl,George R, AU - Sora,Ichiro, PY - 2004/7/1/pubmed PY - 2004/12/16/medline PY - 2004/7/1/entrez SP - 1790 EP - 9 JF - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology JO - Neuropsychopharmacology VL - 29 IS - 10 N2 - 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-HT(ex)) 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/SERT 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 GBR12909 increase 5-HT(ex) 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-HT(ex) 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. SN - 0893-133X UR - https://www.unboundmedicine.com/medline/citation/15226739/Regional_differences_in_extracellular_dopamine_and_serotonin_assessed_by_in_vivo_microdialysis_in_mice_lacking_dopamine_and/or_serotonin_transporters_ DB - PRIME DP - Unbound Medicine ER -