[Dopamine receptor knockout mice]

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.