The D3 dopamine receptor has been proposed as a site of anti-psychotic drug action. The purpose of this study is to determine cellular mechanisms activated upon D3 receptor stimulation or inhibition using complementary in vivo and in vitro approaches. First, the signaling pathway from the D3 receptor to Fos protein expression will be determined. In vivo, Fos protein expression in specific brain areas will be characterized in detail using immunocytochemistry. Mechanistic studies will be done in vitro by transfecting the human D3 receptor gene construct and the c-fos promoter- luciferase fusion gene construct into a neuronal cell line (IMR-32). Then, I will determine whether neurotensin expression is modulated by the D3 receptor. In vivo, changes in neurotensin mRNA will be assessed by in situ hybridization. Mechanistic studies will be done in vitro by transfecting the human D3 receptor gene construct and the neurotensin promoter- luciferase fusion gene construct into a neuronal cell line (IMR-32). The hypothesis is that D3 dopamine receptors modulate neurotensin biosynthesis in specific brain areas through a Fos dependent pathway. This data will help us understand the physiological function of the D3 receptor and its in anti-psychotic drug action.
