Long-term unilateral noradrenergic denervation: monoamine content and 3H-prazosin binding sites in rat neocortex

Direct biochemical determinations of alpha 1 adrenoceptor sites were performed in the neocortex of rats subjected to a selective unilateral noradrenergic deafferentation, obtained by microinjecting 6-OHDA in the right dorsal noradrenergic bundle (DNB). After 3 months survival the alpha 1 sites were assayed using 3H-Prazosin (3H-PRZ), in both the denervated and the contralateral (control) cortex. The catecholamines dopamine (DA), epinephrine (EPI), norepinephrine (NE), as well as the indoleamine serotonin (5-HT) were measured using radioenzymatic assays in samples of the frontal cortex of these same animals, as well as in the septum and hippocampus in order to assess the extent and specificity of the deafferentation. The results document that unilateral NE-deafferentations of the cerebral cortex are feasable, the reduction in NE persists for at least three months, and there is an increased endogenous DA content. In the denervated cerebral cortex specific binding of 3H-PRZ showed an increase (+ 45%) in the density of receptor sites (Bmax) without any changes in the dissociation constant (KD 25 degrees C). The results have to be considered in relation both to plasticity changes in monoamine fibers and to denervation-induced alterations of the postysynaptic alpha-adrenoceptors.