Autoradiographic analysis of adrenergic receptors in the mammalian brain

Noradrenaline (NA) exerts its physiological and pharmacological effects in the central nervous system by interacting with specific receptor sites which are divided into four subtypes, namely alpha-1, alpha-2, beta-1 and beta-2 adrenoceptors. Alpha-1 and beta-1 receptors are thought to be neuronal and post-synaptic, whereas alpha-2-R are neuronal pre- and postsynaptic and beta-2-R have a non neuronal (glial, vascular) localization. The autoradiographic localization of adrenergic receptors is requisite to a better understanding of adrenergic modulation in the nervous system. It complements analyses of adrenergic fibers and terminals and allows comparisons between afferent transmission and various receptor systems. In addition, receptor autoradiography is a preliminary step towards non invasive, in vivo receptor imaging using positron emission tomography (PET). Classical autoradiographic methods using tritium-labeled ligands are relatively tedious, as they require exposure times of several months. In order to circumvent these difficulties, an autoradiographic procedure was developed for visualization of I-125-labeled ligands. The method is validated by its application to the analysis of neuronal postsynaptic (alpha-1 and beta-1) adrenoceptors, in ferret visual cortex, in the forebrain of normal and reeler mutant mice and in the embryonic mouse brain. Distributions of alpha-1 and beta-1 adrenoceptors are studied using revelation of HEAT and ICYP binding sites, respectively. The cerebral cortex of ferret was chosen because it is widely used in vision research. The density of both alpha-1 and beta-1 adrenoceptors shows laminar heterogeneities. Beta-receptors are most heavily concentrated in cortical layers I, II and III, but very low in layer IV and moderately represented in layers V and VI. In contrast, alpha-1 receptors are more diffusely distributed, although preferentially concentrated in layer IV and, to a lesser extent, in upper cortical laminae. The two adrenoceptors are thus segregated in the radial dimension of the cortex, following distributions which are nearly complementary. These observations suggest that alpha- and beta-adrenoceptors might be associated with different stages and/or modes of information processing in the primary visual area. Adrenoceptor distribution was mapped in normal and reeler mice, in order to correlate receptor patterns with architectonic anomalies known to exist in reeler mutant mice. In normal mice, beta-1-receptors predominate in striatum, cortical layers I to III, hippocampal regio superior and some thalamic nuclei; they are moderately concentrated in cortical layers V and VI and poorly represented in lamina IV.(ABSTRACT TRUNCATED AT 400 WORDS)