The long term objectives of the current proposal aim at providing rational pharmacological therapies to be used within existing rehabilitation procedures to promote recovery of lost behavioral capacity. Recent evidence has indicated that agonists and antagonists of catecholamines, in particular norepinephrine, pay an important role in accelerating, retarding, or reversing recovery of function following cortical injury. However, a direct test of the extent of involvement of the noradrenergic system, i.e., the locus ceruleus, is lacking. The present proposal addresses this problem by localized infusions of NE into various brain areas following a unilateral sensorimotor cortex injury that are terminal field projection sites of the locus ceruleus. To further substantiate the role of the locus ceruleus, 6-OHOA lesions of this nucleus will be induced prior to sensorimotor cortex injury and subsequent localized microinfusions of NE. The effect of these treatments will be correlated with the extent of recovery of behavioral function.
