INVESTIGADORES
FALZONE Tomas Luis
artículos
Título:
Enhanced expression of dopamine D(1) and glutamate NMDA receptors in dopamine D(4) receptor knockout mice
Autor/es:
GAN L; FALZONE T; ZHANG G; RUBINSTEIN M,; BALDESSARINI R; TARAZI F
Revista:
JOURNAL OF MOLECULAR NEUROSCIENCE : MN.
Editorial:
Humana Press
Referencias:
Lugar: New York, USA; Año: 2004 vol. 22 p. 167 - 178
ISSN:
0895-8696
Resumen:
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.