Physiological and Anatomical Determinants of Locus Coeruleus Discharge:
Behavioral and Clinical Implications
R. J. Valentino and G. S. Aston-Jones
Division of Behavioral Neurobiology
Department of Mental Health Sciences
Hahnemann University Medical School
Philadelphia, Pennsylvania 19102.
1. Abercrombie ED, Keller RW, Zigmond MJ. Characterization of hippocampal norepinephrine release as measured by microdialysis perfusion: pharmacological and behavioral studies. Neuroscience 1988;27:897–904.
2. Akaoka H, Aston-Jones G. Opiate withdrawal-induced hyperactivity of locus coeruleus neurons is substantially mediated by augmented excitatory amino acid input. J Neurosci 1991;11:3830–3839.
3. Akaoka H, Aston-Jones G. Indirect serotonergic agonists attenuate neuronal opiate withdrawal. Neuroscience 1993;54:561–565.
4. Aoki C. Beta-adrenergic receptors: astrocytic localization in the adult visual cortex and their relation to catecholamine axon terminals as revealed by electron microscope immunohistochemistry. J Neurosci 1992;12:781–792.
5. Aston-Jones G, Akaoka H, Charlety P, Chouvet G. Serotonin selectively attenuates glutamate-evoked activation of noradrenergic locus coeruleus neurons. J Neurosci 1991;11:760–769.
6. Aston-Jones G, Shipley MT, Chouvet G, Ennis M, Van Bockstaele, EJ, Pieribone V, Shiekhattar R, Akaoka H, Drolet G, Astier B, Charlety P, Valentino R, and Williams JT. Afferent regulation of locus coeruleus neurons: anatomy, physiology and pharmacology. Prog Brain Res 1991;85:47–75.
7. Bird SJ, Kuhar MJ. Iontophoretic application of opiates to the LC. Brain Res 1977;122:523–533.
8. Brun P, Suaud-Chagny MF, Lachuer J, Gonon F, Buda M. Catecholamine metabolism in locus coeruleus neurons: a study of its activation by sciatic nerve stimulation in the rat. Eur J Neurosci 1991;3:397–406.
9. Christie MJ, Williams JT, North RA. Cellular mechanisms of opioid tolerance: studies in single brain neurons. Mol Pharmacol 1987;32:633–638.
10. Curtis AL, Conti E, Valentino RJ. Cocaine effects on brain noradrenergic neurons of anesthetized and unanesthetized rats. Neuropharmacology 1993;32:419–428.
11. Descarries L, Watkins KC, and Lapierre Y. Noradrenergic axon terminals in the cerebral cortex of rat. III. Topometric ultrastructural analysis. Brain Res 1977;133:197–222.
12. De Souza EB. Corticotropin-releasing factor receptors in the rat central nervous system: characterization and regional distribution. J Neurosci 1987;7:88–100.
13. De Vries GJ, Buijs RM, Van Leeuwen FW, Caffe AR, Swaab DF. The vasopressinergic innervation of the brain in normal and castrated rats. J Comp Neurol 1985;233:236–254.
14. Eiden LE, Nilaver G, Palkovits M. Distribution of vasoactive intestinal polypeptide (VIP) in the rat brain stem nuclei. Brain Res 1982;231:472–477.
15. Elam M, Svensson TH, Thoren P. Differentiated cardiovascular afferent regulation of locus coeruleus neurons and sympathetic nerves. Brain Res 1985;358:77–84.
16. Engberg G. Nicotine induced excitation of locus coeruleus neurons is mediated via release of excitatory amino acids. Life Sci 1989;44:1535–1540.
17. Foote SL, Bloom FE, Aston-Jones G. Nucleus locus coeruleus: new evidence of anatomical and physiological specificity. Physiol Rev 1983;63:844–914.
18. Forloni G, Grzanna R, Blakely RD, Coyle JT. Co-localization of N-acetyl-aspartyl-glutamate in central cholinergic, noradrenergic, and serotonergic neurons. Synapse 1987;1:455–460.
19. Fritschy J-M, Grzanna R. Distribution of locus coeruleus axons within the rat brainstem demonstrated by PHA-L anterograde tracing in combination with dopamine-b-hydroxylase immunofluorescence. J Comp Neurol 1990;293:616–631.
20. Fritschy J-M, Lyons WE, Mullen CA, Kosofsky BE, Molliver ME, Grzanna R. Distribution of locus coeruleus axons in the rat spinal cord: a combined anterograde transport and immunohistochemical study. Brain Res 1987;437:176–180.
21. Fuxe K, Ganten D, Hokfelt T, Bolme P. Immunohistochemical evidence for the existence of angiotensin II-containing nerve terminals in the brain and spinal cord in the rat. Neurosci Lett 1976;2:229–234.
22. Gagne C, Moyse E, Kocher L, Bour H, Pujol JF. Light microscopic localization of somatostatin binding sites in the locus coeruleus of the rat. Brain Res 1990;530:196–204.
23. Gold MS, Pottash AC. The neurobiological implications of clonidine HCl. Ann NY Acad Sci 1981;362:191–202.
24. Gold PW, Goodwin FK, Chrousos GP. Clinical and biochemical manifestations of depression. N Engl J Med 1988;319:413–420.
25. Grilly DM, Grogan TW. Cocaine and levels of arousal: effects on vigilance task performance of rats. Pharmacol Biochem Behav 1990;35:269–271.
26. Groves PM, Wilson CJ. Monoaminergic presynaptic axons and dendrites in rat locus coeruleus seen in reconstructions of serial sections. J Comp Neurol 1980;193:853–862.
27. Guyenet PG, Aghajanian GK. Acetylcholine Substance P and metenkephalin in the LC: pharmacological evidence for independent sites of action. Eur J Pharmacol 1979;53:319–328.
28. Hajos M, Engberg G. Role of primary sensory neurons in the central effects of nicotine. Psychopharmacology 1988;94:468–470.
29. Heureux RL, Dennis T, Curet O, Scatton B. Measurement of endogenous noradrenaline release in the rat cerebral cortex in vivo by transcortical dialysis: effects of drugs affecting noradrenergic transmission. J Neurochem 1986;46:1794–1801.
30. Hodge CJ, Apkarian AV, Stevens RT, Vogelsang GD, Wisnicki HJ. Locus coeruleus modulation of dorsal horn unit responses to cutaneous stimulation. Brain Res 1981;240:415–420.
31. Hokfelt T, Fuxe K, Goldstein M, Johansson O. Immunohistochemical evidence for the existence of adrenaline neurons in the rat brain. Brain Res 1974;66:235–251.
32. Jacobs BL. Central monoaminergic neurons: single-unit studies in behaving animals. In: Meltzer HY, ed. Psychopharmacology: the third generation of progress. New York: Raven Press, 1987;159–170.
33. Jimenez-Rivera CA, Waterhouse BD. Effects of systemically and locally applied cocaine on cerebrocortical neuron responsiveness to afferent synaptic inputs and glutamate. Brain Res 1991;546:287–296.
34. Johansson O, Hokfelt T, Elde RP. Immunohistochemical distribution of somatostatin-like immunoreactivity in the central nervous system of the adult rat. Neuroscience 1984;13:265–339.
35. Jones SL, Gebhart GF. Characterization of coeruleospinal inhibition of the nociceptive tail-flick reflex in the rat: mediation by spinal alpha 2-adrenoceptors. Brain Res 1986;364:315–330.
36. Jones SL, Gebhart GF. Inhibition of spinal nociceptive transmission from the midbrain, pons and medulla in the rat: activation of descending inhibition by morphine, glutamate and electrical stimulation. Brain Res 1988;460:281–296.
37. Khachaturian H, Lewis M, Watson SJ. Enkephalin systems in the diencephalon and brainstem of the rat. J Comp Neurol 1983; 220:310–320.
38. Ljungdahl A, Hokfelt T, Nilsson G. Distribution of substance P-like immunoreactivity in the central nervous system of the rat. I. Cell bodies and nerve terminals. Neuroscience 1978;3:63–80.
39. Maldonado R, Koob GF. Destruction of the locus coeruleus decreases physical signs of opiate withdrawal. Brain Res 1993; 605:128–138.
40. Maldonado R, Stinus L, Gold LH, Koob GF. Role of different brain structures in the expression of the physical morphine-withdrawal syndrome. J Pharmacol Exp Ther 1992;261:669–677.
41. Marrocco RT, Lane RF, McClurkin JW, Blaha CD, Alkire MF. Release of cortical catecholamines by visual stimulation requires activity in thalamocortical afferents of monkey and cat. J Neurosci 1987;7:2756–2767.
42. Martin JL, Dietl MM, Hof PR, Palacios JM, Magistretti PJ. Autoradiographic mapping of [mono[125I]iodo-Tyr10, MetO17] vasoactive intestinal peptide binding sites in the rat brain. Neuroscience 1987;23:539–565.
43. Mendelsohn FAO, Quirion R, Saavedra JM, Aguilera G, Catt KJ. Autoradiographic localization of angiotensin II receptors in rat brain. Proc Natl Acad Sci USA 1984;81:1575–1579.
44. Milner TA, Abate C, Reis DJ, Pickel VM. Ultrastructural localization of phenylethanolamine N-methyltransferase-like immunoreactivity in the rat locus coeruleus. Brain Res 1989;478:1–15.
45. Mokha SS, McMillan JA, Iggo A. Descending influences on spinal nociceptive neurones from locus coeruleus: actions, pathway, neurotransmitters and mechanisms. In: Bonica JJ, Lindblom U, Iggo A, eds. Advances in pain research and therapy, vol 5. New York: Raven Press, 1983;387–392.
46. Mugnaini E, Oertel WH. An atlas of the distribution of GABAergic neurons and terminals in the rat CNS as revealed by GAD immunohistochemistry. In: Bjorklund A, Hokfelt T, eds. Handbook of chemical neuroanatomy, vol 4. GABA and neuropeptides in the CNS. Amsterdam: Elsevier Science Publishers, 1985;436–608.
47. Olpe HR, Steinmann MW, Pozza MF, Haas HL. Comparative investigation into the actions of ACTH1–24, somatostatin, neurotensin, substance P and vasopressin on LC neuronal activity in vitro. Naunyn Schmiedebergs Arch Pharmacol 1987;336:434–437.
48. Olschowka JA, Molliver ME, Grzanna R, Rice FL, Coyle JT. Ultrastructural demonstration of noradrenergic synapses in the rat central nervous system by dopamine-beta-hydroxylase immunocytochemistry. J Histochem Cytochem 1981;29:271–280.
49. Papadopoulos GC, Parnavelas JG, Buijs RM. Monoaminergic fibers form conventional synapses in the cerebral cortex. Neurosci Lett 1990;76:275–279.
50. Pickel VM, Joh TH, Reis DJ. A serotonergic innervation of noradrenergic neurons in the nucleus locus coeruleus: demonstration by immunocytochemical localization of the transmitter specific enzymes tyrosine hydroxylase and tryptophan hydroxylase. Brain Res 1977;131:197–214.
51. Pickel VM, Joh TH, Reis DJ, Leeman SE, Miller RJ. Electron microscopic localization of substance P and enkephalin in axon terminals related to dendrites of catecholaminergic neurons. Brain Res 1979;160:387–400.
52. Quirion R, Shults CW, Moody TW, Pert CB, Chase TN, O'Donahue TL. Autoradiographic distribution of substance P receptors in rat central nervous system. Nature 1983;303:714–716.
53. Rasmussen K, Aghajanian GK. Withdrawal-induced activation of locus coeruleus neurons in opiate-dependent rats: attenuation by lesion of the nucleus paragigantocellularis. Brain Res 1989; 505:346–350.
54. Rasmussen K, Beitner-Johnson DB, Krystal JH, Aghajanian GK, Nestler EJ. Opiate withdrawal and rat locus coeruleus: behavioral, electrophysiological, and biochemical correlates. J Neurosci 1990;10:2308–2317.
55. Reddy SV, Maderdrut JL, Yaksh TL. Spinal cord pharmacology of adrenergic agonist-mediated antinociception. J Pharmacol Exp Ther 1980;213:525–533.
56. Rooter A, Birdsall NJM, Field PM, Raisman G. Muscarinic receptors in the central nervous system of the rat. II. Distribution and binding of [3H] propylbenzilylcholine mustard in the midbrain and hindbrain. Brain Res Rev 1979;1:167–183.
57. Ruggiero DA, Giuliano R, Anwar M, Stornetta R, Reis DJ. Anatomical substrates of cholinergic-autonomic regulation in the rat. J Comp Neurol 1990;292:1–53.
58. Shipley MT, Halloran FJ, De La Torre J. Surprisingly rich projection from locus coeruleus to the olfactory bulb in rat. Brain Res 1985;329:294–299.
59. Siever LJ. Role of noradrenergic mechanisms in the etiology of the affective disorders. In: Meltzer HY, ed. Psychopharmacology: the third generation of progress. New York: Raven Press, 1987;493–504.
60. Smith Y, Parent A, Kerkerian L, Pelletier G. Distribution of neuropeptide Y immunoreactivity in the basal forebrain and upper brainstem of the squirrel monkey (Saimiri sciurens). J Comp Neurol 1985;236:71–89.
61. Stokes PE, Sikes CR. Hypothalamic-pituitary-adrenal axis in affective disorders. In: Meltzer HY, ed. Psychopharmacology: the third generation of progress. New York: Raven Press, 1987;589–608.
62. Sutin EL, Jacobowitz DM. Immunocytochemical localization of peptides and other neurochemicals in the rat laterodorsal tegmental nucleus and adjacent area. J Comp Neurol 1988;270:243–270.
63. Svensson TH. Peripheral, autonomic regulation of locus coeruleus noradrenergic neurons in brain: putative implications for psychiatry and psychopharmacology. Psychopharmacology 1987;92:1–7.
64. Uhl GR, Goodman RR, Snyder SH. Neurotensin-containing cell bodies, fibers and nerve terminals in brainstem of the rat: immunohistochemical mapping. Brain Res 1979;167:77–91.
65. Vale W, Spiess J, Rivier C, Rivier J. Characterization of a 41-residue ovine hypothalamic peptide that stimulates secretion of corticotropin and beta-endorphin. Science 1981;213:1394–1397.
66. Valentino RJ, Foote SL, Page ME. The locus coeruleus as a site for integrating corticotropin-releasing factor and noradrenergic mediation of stress responses. Ann NY Acad Sci 1993;697:171–187.
67. Wang YY, Aghajanian GK. Excitation of locus coeruleus neurons by vasoactive intestinal peptide: evidence for a G-protein-mediated inward current. Brain Res 1989;500:107–118.
68. Waterhouse BD, Lin CS, Burne RA, Woodward DJ. The distribution of neocortical projection neurons in the locus coeruleus. J Comp Neurol 1983;217:418–431.
69. Waterhouse BD, Sessler FM, Liu W, Lin C-S. Second messenger-mediated actions of norepinephrine on target neurons in central circuits: a new perspective on intracellular mechanisms and functional consequences. Prog Brain Res 1991;88:351–362.
70. Watson SJ, Richard CW, Barchas JD. Adrenocorticotropin in rat brain: immunohistochemical localization in cells and axons. Science 1978;200:1180–1182.
71. Weissmann-Nanupoulos D, Mach E, Magre J, Demassey Y, Pujol JF. Evidence for the localization of 5HT1A binding sites on serotonin containing neurons in the raphe dorsalis and raphe centralis nucleus of the rat brain. Neurochem Int 1985;7:1061–1072.
72. Xiong H, Marshall KC. Angiotensin II modulation of glutamate excitation of LC neurons. Neurosci Lett 1990;118:261–264.
73. Young WS III, Kuhar MJ. Noradrenergic a1 and a2 receptors: autoradiographic visualization. Eur J Pharmacol 1979;59:317–319.