The goal of the proposed project is to gain an understanding of the factors which regulate development of alpha-2 adrenergic receptor (A2AR) subtypes and their function in the brain. This will be accomplished by defining patterns of development of A2AR in rat brain by quantitative radioligand autoradiography using non-selective and subtype-specific ligands, and subtype-specific antibodies, as well as in situ hybridization to detect mRNAs encoding receptor subtypes. The functional development of these receptor systems will be studied by examining coupling to G-proteins and second messenger systems. Normal function will be disrupted using specific lesions of noradrenergic neurons to gain further insights into factors regulating A2AR development. Hypotheses to be tested are: 1) that development of A2AR subtypes and regulation of this development is region and subtype specific, and 2) that normal development of A2AR, including their function, is dependent on normal noradrenergic innervation during critical periods of development.
