Role of Alpha-2 Adrenorecptors in modulating Cortico-Striatal Activity

Grant Type
Grant Year
Institution Location
Institution Organization Name
Medical University of South Carolina
Investigators Name
Lavin, Antonieta, PhD

The prefrontal cortex, the striatum and the connections between these two brain structures are critically involved in regulating cognitive processes, such as working memory, selective attention and the inhibition of inappropriate responses. Both the prefrontal cortex and the striatum, in turn, receive inputs from structures located in the midbrain. Numerous data have shown that neurotransmitters released from the midbrain [dopamine (DA) and norepinephrine (NE)] are involved in the modulation of the cognitive processes that depend upon the cortico-striatal system. Imaging studies in humans have also suggested that alterations in the function of the corticalstriatal pathway, may underlie the poor response inhibition observed in patients with attention deficit disorder (ADD) and Tourette Syndrome. It is therefore possible that drugs that modulate DA and NE receptors will be effective in modulating behavioral deficits in these conditions. Indeed, noradrenergic agents such as the alpha-2 adrenergic receptor agonists clonidine and guanfacine are used to treat behavioral and cognitive dysfunctions in ADD and Tourette Syndrome; however the cellular mechanisms underlying the therapeutic effects of these drugs are unknown. Thus, the goal of this proposal is to test the hypothesis that alpha-2 agonists modulate the cortico-striatal system. More specifically, we will investigate whether the alpha-2 agonists activate postyspynaptic alpha-2 receptors, and whether by increasing the excitability of these postsynaptic cells, they increase the signal coming to the cortex and the striatum. By investigating the therapeutic effects of alpha-2 agonists on cells in the cortex and the striatum, we will be able to advance our understanding of how attention and working memory operate thus leading to better design of therapeutic agents. Antonieta Lavin, Ph.D. Medical University of South Carolina Charleston, SC Award: $73,652 Tourette Association of America Inc. – Research Grant Award 2007-2008