IBN 98-08657 SCHMAUSS This study uses genetically modified mice with cells that lack two proteins known to be involved in the processing of neurochemical information in the brain. This information is mediated by an important neurotransmitter chemical, dopamine, which is released as a signal by other nerve cells and normally interacts directly with these two receptor proteins. By studying the consequences of a "loss of functions" in these mice, the experiments will define the precise functions of these two receptor proteins. It is known, that both proteins modulate (alter) motor, cognitive, and motivational behavior. However, how they modulate this behavior is still unknown. The study therefore aims to find which particular form of these receptor molecules is targeted to which particular area of nerve cells to be made accessible to dopamine and thus, to mediate specific functions. Furthermore, the expression (occurrence in cells) of other molecules of the brain whose function is tightly associated with the activity of the two receptor proteins that are missing in the genetically modified mice will be studied to determine whether these molecules are also essential for mediating the effects of dopamine. Finally, another series of experiments studies the role of the two receptor proteins for the normal development of the brain. Altogether, the goal of the study is to obtain novel and important information about some of the fundamental biological mechanisms by which the brain processes information that is mediated by one of its major neurotransmitters.
