Dopamine D1 receptor mutant mice are deficient in striatal expression of dynorphin and in dopamine-mediated behavioral responses.
The brain dopaminergic system is a critical modulator of basal ganglia function and plasticity. To investigate the contribution of the dopamine D1 receptor to this modulation, we have used gene targeting technology to generate D1 receptor mutant mice. Histological analyses suggested that there are no major changes in general anatomy of the mutant mouse brains, but indicated that the expression of dynorphin is greatly reduced in the striatum and related regions of the basal ganglia. The mutant mice do not respond to the stimulant and suppressive effects of D1 receptor agonists and antagonists, respectively, and they exhibit locomotor hyperactivity. These results suggest that the D1 receptor regulates the neurochemical architecture of the striatum and is critical for the normal expression of motor activity.
Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge 02139.
M
M
Xu
R
R
Moratalla
L H
LH
Gold
N
N
Hiroi
G F
GF
Koob
A M
AM
Graybiel
S
S
Tonegawa
D000704:Analysis of Variance; D000818:Animals; D001483:Base Sequence; D001552:Benzazepines / Q000494:pharmacology; D001921:Brain / Q000502:physiology*; D002375:Catalepsy / Q000139:chemically induced / Q000503:physiopathology; D002678:Chimera; D003342:Corpus Striatum / Q000378:metabolism*; D003433:Crosses, Genetic; D017931:DNA Primers; D004298:Dopamine / Q000502:physiology*; D004399:Dynorphins / Q000096:biosynthesis*; D005260:Female; D015870:Gene Expression; D006185:Habituation, Psychophysiologic; D007150:Immunohistochemistry; D007395:Interneurons / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D009043:Motor Activity / Q000187:drug effects; D009473:Neuronal Plasticity; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D017447:Receptors, Dopamine D1 / Q000096:biosynthesis / Q000235:genetics*
D001552:Benzazepines; D017931:DNA Primers; D017447:Receptors, Dopamine D1; D004399:Dynorphins; D004298:Dopamine