Hostname: page-component-78c5997874-mlc7c Total loading time: 0 Render date: 2024-11-15T17:54:59.511Z Has data issue: false hasContentIssue false

Response of the Norepinephrine System to Antidepressant Drugs

Published online by Cambridge University Press:  07 November 2014

Abstract

Environmental stimuli and drugs affect the norepinephrine (NE) system and may be linked to the manifestation and treatment of anxiety and affective disorders. The activity of locus ceruleus NE neurons in the brainstem can alter the function offorebrain structures associated with several psychiatric disorders. In particular, NE neurons send and receive projections from sensory afferents, limbic areas, and cortical areas implicated in higher-order brain malfunctions and the symptomatology of anxiety and affective disorders. In turn, anxiolytic and antidepressant drugs are able to offset perturbations of NE activity and forebrain structures with a time course congruent with their therapeutic action. All antide-pressants, even the agents selective for other biogenic amines or peptides, act on the NE system. In the present review, the effects of antidepressants on NE neurons are summarized and applied to the treatment of neuropsychiatric disorders, with emphasis placed on mechanisms of action.

Type
Feature Article
Copyright
Copyright © Cambridge University Press 2001

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

1. Schildkraut, JJ. The biochemical discrimination of subtypes of depressive disorders: an outline of our studies on norepinephrine metabolism and psychoactive drugs in the endogenous depressions since 1967. Pharmacopsychiatria. 1982; 15: 121127.CrossRefGoogle ScholarPubMed
2. Maas, JW. Biogenic amines and depression: biochemical and pharmacological separation of two types of depression. Arch Gen Psychiatry. 1975; 32: 13571361.CrossRefGoogle ScholarPubMed
3. Charney, DS, Heninger, GR. Abnormal regulation of noradrenergic function in panic disorders: effects of clonidine in healthy subjects and patients with agoraphobia and panic disorder. Arch Gen Psychiatry. 1986; 43: 10421054.CrossRefGoogle ScholarPubMed
4. Garvey, MJ, Tollefson, GD, Orsulak, PJ. Elevations of urinary MHPG in depressed patients with panic attacks. J Psychiatr Res. 1987; 20: 183187.CrossRefGoogle ScholarPubMed
5. Roy, A, Dejong, J, Ferraro, T. CSF GABA in depressed patients and normal controls. Psychol Med. 1991; 21: 613618.Google Scholar
6. Grant, SJ, Huang, YH, Redmond, DE Jr. Benzodiazepines attenuate single unit activity in the locus coeruleus. Life Sci. 1980: 27: 22312236.CrossRefGoogle ScholarPubMed
7. Post, RM, Rubinow, DR, Uhde, TW, Roy-Byrne, PP, Linnoila, M, Rosoff, M et al. , Dysphoric mania: clinical and biological correlates. Arch Gen Psychiatry. 1989; 46: 353358.CrossRefGoogle ScholarPubMed
8. Gold, MS. Opiate addiction and the locus coeruleus: the clinical utility of clonidine, naltrexone, methadone, and buprenorphine. Psychiatr Clin North Am. 1993; 16: 6173.CrossRefGoogle ScholarPubMed
9. Manji, HK, Hsiao, JK, Risby, ED et al. , The mechanisms of action of lithium. I. Effects on serotonergic and noradrenergic systems in normal subjects. Arch Gen Psychiatry. 1991; 48: 505512.CrossRefGoogle Scholar
10. Redmond, DE Jr, Huang, YH, Snyder, DR, Maas, JW. Behavioral effects of stimulation of the nucleus locus coeruleus in the stump-tailed monkey Macaca arctoides. Brain Res. 1976; 116: 502510.Google Scholar
11. Abercrombie, ED, Jacobs, BL. Single-unit response of noradrenergic neurons in the locus coeruleus of freely moving cats. I. Acutely presented stressful and nonstressful stimuli. J Neurosci. 1987; 28372843.CrossRefGoogle ScholarPubMed
12. Goddard, AW, Charney, DS. Toward an integrated neurobiology of panic disorder. Clin Psychiatry. 1997; 58: 411.Google ScholarPubMed
13. Southwick, SM, Bremner, JD, Rasmusson, A et al. , Role of norepinephrine in the pathophysiology and treatment of posttraumatic stress disorder. Biol Psychiatry. 1999; 46: 11921204.CrossRefGoogle ScholarPubMed
14. Elam, M, Svensson, TH, Thoren, P. Differentiated cardiovascular afferent regulation of locus coeruleus neurons and sympathetic nerves. Brain Res. 1985; 358: 7784.CrossRefGoogle ScholarPubMed
15. Aben, I, Verhey, F, Honig, A et al. , Research into the specificity of depression after stroke: a review on an unresolved issue. Prog Neuropsychopharmacol Biol Psychiatry. 2001; 25: 671689.CrossRefGoogle Scholar
16. Gold, PW, Chrousos, GP. The endocrinology of melancholic and atypical depression: relation to neurocircuitry and somatic consequences. Proc Assoc Am Physicians. 1999; 111: 2234.CrossRefGoogle ScholarPubMed
17. Aston-Jones, G, Shipley, MT, Chouvet, G et al. , Afferent regulation of locus coeruleus neurons: anatomy, physiology and pharmacology. Prog Brain Res. 1991; 88: 4775.Google Scholar
18. Rasmussen, K, Morilak, DA, Jacobs, BL. Single unit activity of locus coeruleus neurons in the freely moving cat. I. during naturalistic behaviors and in response to simple and complex stimuli. Brain Res. 1986; 371: 324334.CrossRefGoogle ScholarPubMed
19. Sapolsky, RM. Glucocorticoids and hippocampal atrophy in neuropsychiatric disorders. Arch Gen Psychiatry. 2000; 57: 925935.CrossRefGoogle ScholarPubMed
20. Sheline, YI, Wang, PW, Gado, MH, Csernansky, JG, Vannier, MW. Hippocampal atrophy in recurrent major depression. Proc Nad Acad Sci USA. 1996; 93: 39083913.Google Scholar
21. Bremner, JD, Randall, P, Scott, TM, Bronen, RA, Seibyl, JP, Southwick, SM et al. MRI-based measurement of hippocampal volume in patients with combat-related posttraumatic stress disorder. Am J Psychiatry. 1995; 152: 973981.Google Scholar
22. Ogura, A, Morinobu, S, Kawakatsu, S, Totsuka, S, Komatani, A. Changes in regional brain activity in major depression after successful treatment with antidepressant drugs. Acta Psychiatr Scand. 1998; 98: 5459.CrossRefGoogle ScholarPubMed
23. Malberg, JE, Eisch, AJ, Nestler, EJ, Duman, RS. Chronic antidepressant treatment increases neurogenesis in adult rat hippocampus. J Neurosci. 2000; 20: 91049110.Google Scholar
24. Manfro, GG, Otto, MW, McArdle, ET, Worthington, JJ 3rd, Rosenbaum, JF, Pollack, MH. Relationship of antecedent stressful life events to childhood and family history of anxiety and the course of panic disorder. J Affect Disord. 1996; 25: 135139.CrossRefGoogle Scholar
25. Mann, JJ, Aarons, SF, Frances, AJ, Brown, RD. Studies of selective and reversible monoamine oxidase inhibitors. J Clin Psychiatry. 1984; 45: 6266.Google Scholar
26. Blier, P, de Montigny, C. Serotoninergic but not noradrenergic neurons in rat central nervous system adapt to long-term treatment with monoamine oxidase inhibitors. Neuroscience. 1985; 16: 949955.CrossRefGoogle Scholar
27. Sulser, F. Deamplification of noradrenergic signal transfer by antidepr sants: a unified catecholamine-serotonin hypothesis of affective disorders. Psychopharmacol Bull. 1983; 19: 300304.Google Scholar
28. Blier, P, de Montigny, C. Current advances and trends in the treatment of depression. Trends Pharmacol Sci. 1994; 15: 220226.Google Scholar
29. Szabo, ST, de Montigny, C, Blier, P. Progressive attenuation of the firing activity of locus coeruleus noradrenergic neurons by sustained administration of selective 5-HT reuptake inhibitors. Int J Neuropsychopharmacol. 2000; 3: 111.Google Scholar
30. Szabo, ST, Blier, P. Effect of acute and sustained administration of reboxetine on locus coeruleus noradrenergic and dorsal raphe 5-HT neurons. Eur J Neurosci. 2001; 13: 114.Google Scholar
31. Montgomery, SA. The place of reboxetine in antidepressant therapy. J Clin Psychiatry. 1998; 14: 2629.Google Scholar
32. Invernizzi, RW, Parini, S, Sacchetti, G et al. , Chronic treatment with reboxetine by osmotic pumps facilitates its effect on extracellular noradrenaline and may desensitise alpha(2)-adrenoceptors in the prefrontal cortex. Br J Pharmacol. 2001; 132: 183188.CrossRefGoogle ScholarPubMed
33. Sacchetti, G, Bernini, M, Bianchetti, A et al. , Studies on the acute and chronic effects of reboxetine on extracellular noradrenaline and other monoamines in the rat brain. Br J Pharmacol. 1999; 128: 13321338.CrossRefGoogle ScholarPubMed
34. Szabo, ST, Blier, P. Effects of the selective norepinephrine reuptake inhibitor reboxetine on norepinephrine and serotonin transmission in the rat hippocampus. Neuropsychopharmacology. In press.Google Scholar
35. Mongeau, R, Blier, P, de Montigny, C. The serotonergic and noradrenergic systems of the hippocampus: their interactions and the effects of antidepressant treatments. Brain Res Brain Res Rev. 1997; 23: 145195.Google Scholar
36. Meyer, JH, Kapur, S, Houle, S, DaSilva, J, Owczarek, B, Brown, GM et al. , Prefrontal cortex 5-HT2 receptors in depression: an [18F]setoperone PET imaging study. Am J Psychiatry. 1999; 156: 10291034.CrossRefGoogle ScholarPubMed
37. Piletz, JE, Zhu, H, Ordway, G et al. , Imidazoline receptor proteins are decreased in the hippocampus of individuals with major depression. Biol Psychiatry. 2000; 48: 910919.CrossRefGoogle ScholarPubMed
38. Haddjeri, N, Blier, P, de Montigny, C. Acute and long-term actions of the antidepressant drug mirtazapine on central 5-HT neurotransmission. J Affect Disord. 1998; 51: 255266.CrossRefGoogle ScholarPubMed
39. Delgado, PL. Depression: the case for a monoamine deficiency. J Clin Psychiatry. 2000; 6: 711.Google Scholar
40. Haddjeri, N, Blier, P. Effect of neurokinin-I receptor antagonists on the function of 5-HT and noradrenaline neurons. Neuroreport. 2000; 11: 13231327.CrossRefGoogle ScholarPubMed
41. Hyttell, L. Citalopram-pharmacological profile of specific serotonin uptake inhibitor with antidepressant activity. Prog Neuropsychopharnuicol Biol Psychiatry. 1982; 6: 277295.Google Scholar
42. Dong, J, Blier, P. Modification of norepinephrine and serotonin, but not dopamine neuronal firing by bupropion. Psychopharmacology. 2000; 155: 5257.Google Scholar
43. Gobbi, G, Slater, S, Boucher, N, Debonnel, G, Blier, P. Effects of bupropion on nor-epinephrine and serotonin reuptake in healthy human subjects. Soc Neurosci. 2000; 26: 495.3.Google Scholar
44. Wilens, TE, Spencer, TJ, Biederman, J et al. , A controlled clinical trial of bupropion for attention deficit hyperactivity disorder in adults. Am J Psychiatry. 2001; 158: 282288.Google Scholar
45. Szabo, ST, de Montigny, C, Blier, P. Modulation of noradrenergic neuronal firing by selective serotonin reuptake blockers. Br J Pharmacol. 1999; 126: 568571.Google Scholar
46. Freo, U, Ori, C, Dam, M, Merico, A, Pizzolato, G. Effects of acute and chronic treatment with fluoxetine on regional glucose cerebral metabolism in rats: implications for clinical therapies. Brain Res. 2000; 854: 3541.Google Scholar
47. Shiekhattar, R, Aston-Jones, G. Sensory responsiveness of brain noradrenergic neurons is modulated by endogenous brain serotonin. Brain Res. 1993; 623: 7276.CrossRefGoogle ScholarPubMed
48. Charlety, PJ, Chergui, K, Akaoka, H et al. , Serotonin differentially modulates responses mediated by specific excitatory amino acid receptors in the rat locus coeruleus. Eur J Neurosci. 1993; 5: 10241028.Google Scholar
49. Szabo, ST, Blier, P. 5-HT2A antagonism reverses the SSRI mediated attenuation of locus coeruleus norepinephrine neurons. Soc Neurosci. 2000; 26: 721.6Google Scholar
50. Chiang, C, Aston-Jones, G. A 5-hydroxytryptamine2 agonist augments gammaaminobutyric acid and excitatory amino acid inputs to noradrenergic locus coeruleus neurons. Neuroscience. 1993; 54: 409420.CrossRefGoogle ScholarPubMed
51. Szabo, ST, Blier, P. Serotonin1A agonist on the firing activity of LC NA neurons are mediated through Excitatory Amino Acids and GABA. Can Coll Neuropsychopharmacol. 2001.Google Scholar
52. Valentino, RJ, Curtis, AL, Page, ME, Pavcovich, LA, Florin-Lechner, SM. Activation of the locus ceruleus brain noradrenergic system during stress: circuitry, consequences, and regulation. Adv Pharmacol. 1998; 42: 781784.Google Scholar