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[Dopamine receptor knockout mice]
1Division of DNA Biology and Embryo Engineering, University of Tokyo, Japan.
Abstract:
Dopaminergic systems are transmitted by dopamine receptors which couple to GTP binding proteins. Five subtypes of dopamine receptors were so far cloned. To study the functions of each dopamine receptors, mice lacking each of D1R, D2R, D3R and D4R dopamine receptors have been generated. Histological analyses of D1R knockout mice indicated that the expression of dynorphin is reduced in the striatum. In contrast with wild-type mice, D1R knockout mice exhibit a dose dependent decrease in locomotion. D2R knockout mice display a hypoactivity. The expression of enkephalin mRNA in the striatum is increased in the D2R knockout mice. D2R knockout mice showed hyperplastic changes of intermediate lobe of the pituitary and the increased expression of POMC in the pituitary in D2R knockout mice. D3R knockout mice are more active than wild-type mice in a novel environment and they exhibit enhanced behavioral sensitivity to cocaine and amphetamine. D4R knockout mice show a hypoactivity, but they display locomotor supersensitivity to ethanol, cocaine, and methamphetamine. Dopamine synthesis and its conversion to DOPAC are elevated in the dorsal striatum from D4R knockout mice.
Insights
Mice lacking dopamine receptors D1R, D2R, D3R, and D4R show varied motor and behavioral changes. These dopamine receptor knockout mice provide insights into receptor function and associated neurological pathways.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Context:
- Dopaminergic systems are crucial for regulating motor control, reward, and other functions.
- Five dopamine receptor subtypes (D1R-D5R) are known, mediating dopamine's effects.
- Understanding individual receptor functions is essential for neurological research.
Purpose:
- To investigate the specific roles of D1R, D2R, D3R, and D4R by generating and analyzing knockout mouse models.
- To elucidate the downstream effects of dopamine receptor dysfunction on behavior and neurochemistry.
Summary:
- D1R knockout mice showed reduced dynorphin expression and decreased locomotion.
- D2R knockout mice exhibited hypoactivity, increased enkephalin mRNA, and pituitary changes.
- D3R knockout mice displayed increased activity and heightened sensitivity to stimulants.
- D4R knockout mice showed hypoactivity but increased sensitivity to certain drugs and elevated dopamine synthesis.
Impact:
- Provides valuable insights into the distinct physiological and behavioral functions of each dopamine receptor subtype.
- Establishes a foundation for further research into dopamine receptor-related disorders.
- Highlights the complex roles of dopamine receptors in motor control, reward pathways, and drug responses.