Journal of Molecular Neuroscience

, Volume 22, Issue 3, pp 167–177

Enhanced expression of dopamine D1 and glutamate NMDA receptors in dopamine D4 receptor knockout mice

  • Lu Gan
  • Tomas L. Falzone
  • Kehong Zhang
  • Marcelo Rubinstein
  • Ross J. Baldessarini
  • Frank I. Tarazi
Original Article

DOI: 10.1385/JMN:22:3:167

Cite this article as:
Gan, L., Falzone, T.L., Zhang, K. et al. J Mol Neurosci (2004) 22: 167. doi:10.1385/JMN:22:3:167

Abstract

Expression of dopamine ([DA] D1 and D2) and glutamate ([Glu]), (N-methyl-d-aspartic acid [NMDA], α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid [AMPA], and kanaic acid [KA]) receptor types were analyzed autoradiographically in forebrain regions of D4 receptor knockout mice and their wild-type controls. Selective radioligand binding to D4 receptors was virtually absent in D4 receptor knockout mouse brain in contrast to significant specific D4 binding in forebrain tissue of wild-type controls. Labeling of D1 receptors was significantly increased in nucleus accumbens (NAc; 39%) and caudate putamen (CPu; 42%) of D4-knockout mice vs wild-type controls. In addition, NMDA receptor labeling was significantly increased in NAc (31%), CPu (40%), and hippocampal CA1 (21%) and CA3 (25%) regions of D4 knockouts vs wild-type controls. No changes in D2, AMPA or KA receptors were found. The findings suggest that D1, D4, and NMDA receptors might interact functionally and that developmental absence of D4 receptors might trigger compensatory mechanisms that enhance expression of D1 receptors in NAc and CPu, and NMDA receptors in NAc, CPu, and hippocampus. The findings also encourage cautious interpretation of results in knockout mice with targeted absence of specific genes, as complex adaptive changes not directly related to the missing gene might contribute to physiological and behavioral responses.

Index Entries

Autoradiography caudate putamen dopamine receptors D4-receptor genetic knockout glutamate receptors mutant mice 

Copyright information

© Humana Press Inc 2004

Authors and Affiliations

  • Lu Gan
    • 1
    • 2
  • Tomas L. Falzone
    • 3
  • Kehong Zhang
    • 1
    • 2
  • Marcelo Rubinstein
    • 3
  • Ross J. Baldessarini
    • 1
    • 2
  • Frank I. Tarazi
    • 1
    • 2
  1. 1.Mailman Research CenterMcLean Division of Massachusetts General HospitalBelmont
  2. 2.Department of Psychiatry and Neuroscience ProgramHarvard Medical SchoolBoston
  3. 3.Instituto de Investigaciones en Ingenierá Genéca y Biologá Molecular (CONICET)Universidad de Buenos AiresBuenos AiresArgentina

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