Anatomy of brain alpha₁‐adrenergic receptors: In vitro autoradiography with [¹²⁵I]‐heat

Abstract

Much useful information on the localization of alpha 1-adrenergic binding sites has been gained by using tritiated radioligands for in vitro autoradiography. However, the iodinated alpha 1-adrenergic antagonist HEAT [( 2-beta (4-hydroxyphenyl)-ethylaminomethyl)-tetralone], BE 2254), a radioligand with high affinity and specificity, provides autoradiographs with a higher signal to noise ratio. This has allowed us to describe the anatomy of these binding sites in much greater detail than previously possible. Regions showing the highest levels of binding include external plexiform layer of the olfactory bulb, layers Va and Vc of frontoparietal cortex, lateral and central amygdaloid nuclei, thalamus, and inferior olive. Other regions were generally less intensely labeled, with the least evidence of labeling in white matter, such as corpus callosum. Some regions (e.g., hippocampus) had only moderate labeling, but the binding appeared in a discrete pattern that reflected the functional organization of the structure. Although the [125I]-HEAT binding sites were distributed in a pattern similar to that previously reported for [3H]-WB 4101 and [3H]-prazosin, the anatomical detail seen with the iodinated ligand is greater. As a result, an association of alpha 1-adrenergic antagonist binding sites with specific layers in the cortex and with some catecholamine-containing nuclei in the brainstem, such as the locus coeruleus, have been seen for the first time.

Role of α1-Adrenoceptors of the Locus Coeruleus in Self-Stimulation of the Medial Forebrain Bundle

“…That the effect of TER on the threshold frequency was due to its action on the LC and not some neighboring nucleus is supported by the fact that the infusion of the drug some distance away from the LC (0.3 mm or greater) greatly attenuated its effects. This is consistent with the fact that the LC possesses the greatest concentration of a 1 -receptors by far in the rodent dorsal pons (Jones et al, 1985;Stone et al, 2004a). However, this does not mean that a 1 -receptors in other brain regions are not involved in positive reinforcement; in fact, a 1 -agonists injected in the rostral ventrolateral medulla have been found to support CPP (Hirakawa et al, 2000).…”

“…a 1 -Adrenoceptors have a widespread distribution in the CNS and affect behavioral activity from multiple regions. The region whose a 1 -receptors have the greatest effect on behavioral activity is the dorsal pons and most likely in the locus coeruleus (LC), which also has one of the highest densities of these receptors in the brainstem (Stone et al, 2004b;Jones et al, 1985). Furthermore, the LC is a site from which self-stimulation can be elicited (Yadin et al, 1983), is highly sensitive to appetitive operant conditioning (Clayton et al, 2004) and has efferent connections with dopaminergic neurons in the ventral tegmental area (Grenhoff et al, 1993;Mejias-Aponte et al, 2004).…”

Emerging Evidence for a Central Epinephrine-Innervated α1-Adrenergic System that Regulates Behavioral Activation and is Impaired in Depression

“…We have confirmed that there is a moderately high density of a 1 -receptors in the cerebellum of the mouse strain used in the above experiments (male Swiss Webster) (Stone EA, Ahsan R, and Lin Y, unpublished results). As noted above, the nucleus accumbens also possesses a 1 -receptors but at a lower density (Jones et al, 1985).…”

“…It should be noted that two of the above definite sites, the dorsal pons and DR, are known to possess very high densities of a 1 -receptors (Chamba et al, 1991;Jones et al, 1985;Zilles et al, 1993), whereas the cerebellum has been reported by some (Acosta-Martinez et al, 1999;Jones et al, 1985;Zilles et al, 1993), but not others (Palacios et al, 1987), to have a moderately high density. We have confirmed that there is a moderately high density of a 1 -receptors in the cerebellum of the mouse strain used in the above experiments (male Swiss Webster) (Stone EA, Ahsan R, and Lin Y, unpublished results).…”

“…a 1 -Receptors are present in a broad range of structures including most motor, sensory, autonomic, and neuroendocrine-related areas (Acosta-Martinez et al, 1999;Day et al, 1997;Jones et al, 1985;Volgin et al, 2001;Williams and Morilak, 1997;Zilles et al, 1993). They are present at low densities in basal ganglia structures (corpus striatum, nucleus accumbens, ventral tegmental area, substantia nigra), at higher densities in prefrontal and motor cortices, hypothalamus, brainstem motor nuclei, cerebellum, and spinal motorneurons, and at very high densities in the olfactory bulb, thalamus, locus coeruleus (LC), dorsal raphe (DR), piriform cortex, and amygdala.…”