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.
|Essali, Norah; Sanders, Jeff (2016) Interdependent adrenergic receptor regulation of Arc and Zif268 mRNA in cerebral cortex. Neurosci Lett 612:38-42|
|Sanders, J D; Happe, H K; Bylund, D B et al. (2011) Changes in postnatal norepinephrine alter alpha-2 adrenergic receptor development. Neuroscience 192:761-72|
|Sanders, J D; Happe, H K; Bylund, D B et al. (2008) Differential effects of neonatal norepinephrine lesions on immediate early gene expression in developing and adult rat brain. Neuroscience 157:821-32|
|Sanders, Jeff D; Szot, Patricia; Weinshenker, David et al. (2006) Analysis of brain adrenergic receptors in dopamine-beta-hydroxylase knockout mice. Brain Res 1109:45-53|
|Sanders, Jeff D; Happe, H Kevin; Murrin, L Charles (2005) A transient expression of functional alpha2-adrenergic receptors in white matter of the developing brain. Synapse 57:213-22|
|Bylund, D B; Murrin, L C (2000) Radioligand saturation binding experiments over large concentration ranges. Life Sci 67:2897-911|
|Kable, J W; Murrin, L C; Bylund, D B (2000) In vivo gene modification elucidates subtype-specific functions of alpha(2)-adrenergic receptors. J Pharmacol Exp Ther 293:7-Jan|