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Central Noradrenergic Receptors: Localization, Function and Molecular Mechanisms

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New Concepts in Neurotransmitter Regulation

Abstract

Fluorescence histochemical data make it eminently clear that the catecholamine-containing neurons of the brain are restricted to a relatively small region of the pons and mesencephalon and yet send very discrete axonal tracts to spinal cord, diencephalon and cortices. In order to determine the effects of norepinephrine (NE) on postsynaptic neurons and the changes in these effects produced by drugs which influence behavior, the location and function of the presumed NE-mediated synapses must be determined for each of the regions receiving these fibers. Such data has now been accumulated in detail for the NE projection to the cerebellum (see below) and has been partially elucidated for several other regions. This paper will describe the methods now being used in our laboratory to determine the localization and function of NE-mediated synapses.

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References

  • Aghajanian, G. K. 1972. LSD and CNS transmission. Ann. Rev. Pharmacol. 12: 157.

    Article  PubMed  CAS  Google Scholar 

  • Aghajanian, G. R. and Bloom, F. E. 1967. Electron-microscopic localization of tritiated norepinephrine in rat brain effects of drugs. Pharmacol. Exp. Ther. 156: 407.

    CAS  Google Scholar 

  • Barker, J. L., Crayton, J. C., and Nicoll, R. A. 1971. Supraoptic neurosecretory cells: Adrenergic and cholinergic sensitivity. Science 171: 208.

    Article  PubMed  CAS  Google Scholar 

  • Bloom, F. E. 1968. Electrophysiological pharmacology of single nerve cells. In: Psychopharmacology, A 10 Year Progress Report (Ed. Effron, D.H.) Washington, D.C.: U.S. Govt. Printing Office.

    Google Scholar 

  • Bloom, F. E. 1971. Fine structural changes in rat brain after intracisternal injection of 6-hydroxydopamine. In: 6-Hydroxydopamine (Eds. Malmors, T. and Thoenen, H.) Amsterdam: North Holland Publishing Co., pp. 135.

    Google Scholar 

  • Bloom, F. E. and Costa, E. 1971. The effects of drugs on serotonergic nerve terminals. In: Advances in Cytopharmacology (Ed. Edelson, E.) New York: Raven Press, Vol. I., pp. 379.

    Google Scholar 

  • Bloom, F. E., von Baumgarten, R., Oliver, A. P., Costa, E. and Salmioraghi, G.C. 1964 a. Microelectrophoretic studies on adrenergic mechanisms of rabbit olfactory bulb neurons. Life Sci. 3: 131.

    Article  PubMed  CAS  Google Scholar 

  • Bloom, F. E., Costa, E. and Salmoiraghi, G. C. 1964 b. Analysis of individual rabbit olfactory bulb neuron response to microelectrophoresis of acetylcholine, norepinephrine and serotonin synergists and antagonists. Pharmacol. Exp. Ther. 146: 16.

    CAS  Google Scholar 

  • Bloom, F. E., Hoffer, B. J. and Siggins, G. R. 1971 Studies on norepinephrine-containing afferents to Purkinje cells of rat cerebellum: I. Localization of the fibers and their synapses. Brain Res. 25: 501.

    Article  PubMed  CAS  Google Scholar 

  • Bloom, F. E., Battenberg, E., Hoffer, B. J., Siggins, G. R., Steiner, A.L., Parker, C.W. and Wedner, H. J. 1972. Noradrenergic stimulation of cyclic adenosine monophosphate in rat Purkinje neurons. Science (submitted for publication).

    Google Scholar 

  • Bloom, F. E., Hoffer, B. J. and Siggins, G. R. 1972. Norepinephrine mediated synapses: A model system for neuropsychopharmacology. Biol. Psychiat. 4(2): 157.

    PubMed  CAS  Google Scholar 

  • Boakes, R. J., Bradley, P. B., Brookes, N., Candy, J. M. and Wolstencroft J. H. 1971. Actions of noradrenaline, other sympathomimetic amines and antagonists on neurones in the brainstem of the cat. Brit. J. Pharmacol. 41: 262.

    Google Scholar 

  • Bradley, P. B. and Wolstencroft, J. H. 1962. Excitation and inhibition of brainstem neurones by noradrenaline and acetylcholine. Nature 196: 840.

    Article  PubMed  CAS  Google Scholar 

  • Breckenridge, B. 1964. The measurement of cyclic adenylate in tissues. Proc. Nat. Acad. Sci. 52: 1580.

    Article  PubMed  CAS  Google Scholar 

  • Butcher, R. W. and Baird, C. E. 1968. Effects of prostaglandins on adenosine 3′,5′-monophosphate levels in fat and other tissues. J. Biol. Chem. 243: 1713.

    PubMed  CAS  Google Scholar 

  • Chu, N-S. and Bloom, F. E. 1972. Single neuron activity of the norepinephrine-containing locus coeruleus nucleus of the brainstem in the cats. Fed. Proc. 31: 377.

    Google Scholar 

  • Couch, J.R. 1970. Responses of neurons in the raphe nuclei to serotonin, norepinephrine and acetylcholine and their correlation with an excitatory synaptic input. Brain Res. 19: 137.

    Article  PubMed  CAS  Google Scholar 

  • Crayton, J. C. and Bloom, F. E. 1969. Responsiveness of cat raphe nucleus to microelectrophoresis of norepinephrine and serotonin. Anat. Rec. 163: 173.

    Google Scholar 

  • Cowan, M. W., Gottlieb, D. I., Hendrickson, A. E., Price, J. L. and Woolsey, T. A. 1972. The autoradiographic demonstration of axonal connections in the central nervous system. Brain Res. 37: 21.

    Article  PubMed  CAS  Google Scholar 

  • Dahlström, A. and Fuxe, K. 1964. Evidence for the existence of monoamine-containing cell bodies. Acta. Physiol. Scand. 62:Suppl. 232.

    Google Scholar 

  • Dahlström, A., Fuxe, K., Olson, L. and Ungerstedt, U. 1965. On the distribution and possible function of monoamine nerve terminals in the olfactory bulb of the rabbit. Life Sci. 4: 2071

    Article  PubMed  Google Scholar 

  • Falck, B., Hillarp, N-A., Thieme, G. and Torp, A. 1962. Fluorescence of catecholamines and related compounds condensed with formaldehyde. J. Histochem. Cytochem. 10: 348.

    Article  CAS  Google Scholar 

  • Frederickson, R.C.A., Jordan, L.M. and Phillis, J.W. 1971. The action of noradrenaline on cortical neurons: effect of. Brain Res. 35: 556.

    Article  PubMed  CAS  Google Scholar 

  • Fuxe, F., Hokfelt, T. and Ungerstedt, U. 1970. Morphological and functional aspects of central monoamine neurons. Int. Rev. Neurobiol. 13: 93.

    Article  CAS  Google Scholar 

  • Glowinski, J. and Baldessarini, R. J. 1966. Metabolism of norepinephrine in the central nervous system. Pharmacol. Rev. 18: 1201.

    PubMed  CAS  Google Scholar 

  • Hebb, C. 1970. CNS at the cellular level: identity of transmitter agents. Ann. Rev. Physiol. 32: 165.

    Article  CAS  Google Scholar 

  • Hoffer, B. J., Siggins, G. R. and Bloom, F. E. 1971 a. Studies on norepinephrine-containing afferents to Purkinje cells of rat cerebellum: II. Sensitivity of Purkinje cells to norepinephrine and related substances administered by microiontophoresis. Brain Res. 25: 523.

    Article  PubMed  CAS  Google Scholar 

  • Hoffer, B. J., Siggins, G. R., Oliver, A. P. and Bloom, F.E. 1971 b. Cyclic AMP mediation of norepinephrine inhibition in rat cerebellar cortex: A unique class of synaptic responses. Ann. N.Y. Acad. Sci. 185: 531.

    Article  PubMed  CAS  Google Scholar 

  • Hoffer, B. J., Chu, N-s., and Oliver, A. P. 1972. Cytochemical and electrophysiological studies on central catecholamine-containing neurons. Proc. Vth Intl. Congress Pharmacol., pp. 103.

    Google Scholar 

  • Hökfelt, T. 1967. Electron microscopic studies on brain slices from regions rich in catecholamine terminals. Acta. Physiol. Scand. 69: 119.

    Article  PubMed  Google Scholar 

  • Hökfelt, T. 1968. In vitro studies on central and peripheral monoamine neurons at the ultrastructural level. Z. Zellforsch. 91: 1.

    Article  PubMed  Google Scholar 

  • Hökfelt, T. 1972. Ultrastructural localization of intra-neuronal monoamines - some aspects on methodology. Prog. Brain Res. 34: 213.

    Article  Google Scholar 

  • Hökfelt, T. and Fuxe, K. 1969. Cerebellar monoamine nerve terminals, a new type of afferent fiber to the cortex cerebelli. Exp. Brain Res. 9: 63.

    Article  PubMed  Google Scholar 

  • Iversen, L.L. 1967. The Uptake and Storage of Noradrenaline in Sympathetic Nerves, Cambridge University Press.

    Google Scholar 

  • Iversen, L. L. and Uretsky, N. J. 1971. Biochemical effects of 6-hydroxydopamine on catecholamine-containing neurons in the rat central nervous system. In: 6-Hydroxydopamine. (Eds. Malmfors, T. and Thoenen, H.) Amsterdam: North Holland Publishing Co., pp. 171.

    Google Scholar 

  • Johnson, E. S., Roberts, M.H.T., Sobieszek, A. and Straughan, D.W. 1969 a. Noradrenaline sensitive cells in cat cerebral cortex. Int. J. Neuropharmacol. 8: 549.

    Article  PubMed  CAS  Google Scholar 

  • Johnson, E. S., Roberts, M.H.T. and Straughan, D. W. 1969 b. The responses of cortical neurones to monoamines under differing anaesthetic conditions. J. Physiol (Lond) 203: 261.

    CAS  Google Scholar 

  • Jones, B. E., Bobillier, P. and Jouvet, M. 1969. Effects de la destruction des neurones contenant des catecholamines du mesencephale sur le cycle veille sommeils du chat. C. R. Soc. Biol. Paris 163: 176.

    PubMed  CAS  Google Scholar 

  • Jouvet, M. 1969. Biogenic amines and the state of sleep. Science 163: 32.

    Article  PubMed  CAS  Google Scholar 

  • Kakiuchi, S. and Rall, T. W. 1968. The influence of chemical agents on the accumulation of adenosine 3′,5′-phosphate in slices of rabbit cerebellum. Molec. Pharmacol. 4: 367.

    CAS  Google Scholar 

  • Krishna, G., Weiss, B. W., Davies, J. L. and Hynie, S. 1966. Mechanism of nicotinic acid inhibition of hormone-indueed lipolysis. Fed. Proc. 25: 719.

    Google Scholar 

  • Krnjevic, K. and Phillis, J. W. 1963 a. Actions of certain amines on cerebral cortical neurones. Brit. J. Pharmacol. 20: 471.

    PubMed  CAS  Google Scholar 

  • Krnjevic, K. and Phillis, J. W. 1963 b. Iontophoretic studies of cortical neurones in the mammalian cerebral cortex. J. Physiol. (Lond) 165: 274.

    CAS  Google Scholar 

  • Kukovetz, W. R. and Poch, G. 1970. Cardiostimulatory effects of cyclic 3′,5′-adenosine monophosphate and its acylated derivatives. Naunyn-Schmiedeberg Arch. Pharmak. 266: 236.

    Article  CAS  Google Scholar 

  • Larramendi, L.M.H. 1969. Analysis of synaptogenesis in the cerebellum of the mouse. In: Neurobiology of Cerebellar Evolution and Development. (Ed. Llinas, R.) Chicago: Amer. Med. Ass. Press, pp. 803.

    Google Scholar 

  • Lenn, N. J. 1967. Localization of uptake of tritiated norepinephrine by rat brain in vivo and in vitro using electron microscopy. Amer. J. Anat. 120: 377.

    Article  Google Scholar 

  • Lish, P. M., Weikel, J. H. and Dugan, K. W. 1965. Pharmacological and toxicological properties of two new β-adrenergic receptor antagonists. J. Pharmacol. Exp. Ther. 149: 161.

    PubMed  CAS  Google Scholar 

  • Loizou, L. A. 1969. Projections of the nucleus locus coeruleus in the albino rat. Brain Res. 15: 563.

    Article  PubMed  CAS  Google Scholar 

  • Malmfors, T. and Thoenen, H. (Eds.) 1971. 6-Hydroxydopamine and Catecholamine Neurons. Amsterdam: North Holland Publishing Co., pp. 368.

    Google Scholar 

  • Nelson, C. N., Hoffer, B. J., and Bloom, F. E. 1972. Evidence for monoamine inputs to frontal polysensory cortex in the squirrel monkey. Fed. Proc. 31: 270.

    Google Scholar 

  • Nelson, J., Sheu, Y-s. and Bloom, F. E. 1972. A chronic microelectrode advancer (in preparation).

    Google Scholar 

  • Nicoli, R. A. and Barker, J. L. 1971. The pharmacology of recurrent inhibition in the supraoptic neurosecretory system. Brain Res. 35: 501.

    Article  Google Scholar 

  • O′Leary, J. L., Petty, J., Smith, J. M., O′Leary, M. and Inukai, J. 1968. Cerebellar cortex of rat and other animals. A structural and ultrastructurai study. Comp. Neurol. 134: 401.

    Article  Google Scholar 

  • Olson, L. and Fuxe, K. 1971. On the projections from the locus coeruleus noradrenaline neurons. Brain Res. 28: 165.

    Article  PubMed  CAS  Google Scholar 

  • Richardson, K. C. 1966. Electron microscopic identification of autonomic nerve fibers. Nature 210: 756.

    Article  PubMed  CAS  Google Scholar 

  • Salmoiraghi, G. C. and Bloom, F. E. 1964. The pharmacology of individual neurons. Science 144: 493.

    Article  PubMed  CAS  Google Scholar 

  • Salmoiraghi, G. C. and Stefanis, C. 1967. A critique of iontophoretic studies of central nervous system neurons. Int. Rev. Neurobiol. 10: 1.

    Article  PubMed  CAS  Google Scholar 

  • Salmoiraghi, G. C. and Weight, F. F. 1967. Micromethods in neuropharmacology: An approach to the study of anesthetics. Anesthesiology 28: 54.

    Article  PubMed  CAS  Google Scholar 

  • Salmoiraghi, G. C., Bloom, F. E. and Costa, E. 1964. Adrenergic mechanisms in rabbit olfactory bulb. Am. J. Physiol. 207: 1417.

    PubMed  CAS  Google Scholar 

  • Siggins, G. R., Hoffer, B. J. and Bloom, F. E. 1969. Cyclic adenosine monophosphate: Possible mediator for norepinephrine effects on cerebellar Purkinje cells. Science 165: 1018.

    Article  PubMed  CAS  Google Scholar 

  • Siggins, G. R., Hoffer, B. J. and Bloom, F. E. 1971 a. Studies on norepinephrine-containing afferents to Purkinje cells of rat cerebellum. III. Evidence for mediation of norepinephrine effects by cyclic 3′ 5′-adenosine monophosphate. Brain Res. 25: 535.

    Article  PubMed  CAS  Google Scholar 

  • Siggins, G. R., Hoffer, B. J. and Bloom, F. E. 1971 b. Prostaglandin norepinephrine interactions in brain: Microelectrophoretic and histochemical correlates. Ann. N.Y. Acad. Sci. 180: 302.

    Article  PubMed  CAS  Google Scholar 

  • Siggins, G. R., Oliver, A. P., Hoffer, B. J. and Bloom, F. E. 1971 c. Cyclic adenosine monophosphate and norepinephrine: Effects on transmembrane properties of Purkinje cells. Science 171: 192.

    Article  PubMed  CAS  Google Scholar 

  • Siggins, G. R., Hoffer, B. J., Oliver, A. P. and Bloom, F. E. 1971 d. Activation of a central noradrenergic projection to cerebellum. Nature 233: 481.

    Article  PubMed  CAS  Google Scholar 

  • Snyder, S. H., Taylor, K. M., Coyle, J. T. and Meyerhoff, J. L. 1970. The role of brain dopamine in behavioral regulation and the actions of psychotropic drugs. Amer. J. Psychiat. 127: 117.

    Google Scholar 

  • Stone, T.W. 1971. Are noradrenaline excitations artifacts? Nature 234: 145.

    Article  PubMed  CAS  Google Scholar 

  • Sutherland, E. W., Rall, T. W. and Menon, T. 1962. Adenyl cyclase. I. Distribution, preparation and properties. Biol. Chem.237: 1220.

    CAS  Google Scholar 

  • Sutherland, E. W., Robinson, G. A. and Butcher, R. 1968. Some aspects of the biological role of adenosine 3′,5′-monophosphate. Circulation 3: 279.

    Google Scholar 

  • Ungerstedt, U. 1971. Stereotaxic mapping of the monoamine pathways in the rat brain. Acta. Physiol. Scand. Suppl. 367.

    Google Scholar 

  • Wedner, H. J., Hoffer, B. J., Battenberg, E., Steiner, A. L., Parker, C. W. and Bloom, F.E. 1972. A method for detecting intracellular cyclic adenosine monophosphate by immunofluorescence. J. Histochem. Cytochem. (in press).

    Google Scholar 

  • Weight, F. F. 1971. Mechanisms of synaptic transmission. Neurosciences Res. 4:1.

    CAS  Google Scholar 

  • Weiss, B. and Kidman, A.D. 1969. Neurobiological significance of cyclic 3′5′-adeonsine monophosphate. In: Advances in Biochemical Psychopharmacology (Eds. Costa, E. and Greengard, P.) New York: Raven Press, Vol. 1, pp. 131.

    Google Scholar 

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Bloom, F.E., Hoffer, B.J., Siggins, G.R. (1973). Central Noradrenergic Receptors: Localization, Function and Molecular Mechanisms. In: Mandell, A.J. (eds) New Concepts in Neurotransmitter Regulation. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-4574-9_11

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  • DOI: https://doi.org/10.1007/978-1-4613-4574-9_11

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