THE ROLE OF INTERACTIONS BETWEEN BRAIN NEUROTRANSMITTERS IN PATHOPHYSIOLOGY AND TREATMENT OF AFFECTIVE DISORDERS

  • E. Dremencov Institute of Molecular Physiology and Genetics, Slovak Academy of Sciences, Bratislava, Slovakia; Institute of Experimental Endocrinology, Biomedical Research Center, Slovak Academy of Science, Bratislava, Slovakia; Neuroken Consulting, Groningen, the Netherlands eliyahu.dremencov@savba.sk
Keywords: serotonin (5-HT), norepinephrine, dopamine, glutamate, GABA, neuropeptides, hypothalamus, hippocampus, voltage-dependent calcium channels

Abstract

Aim of the review is to summarize the contemporary evidences on interactions between brain neurotransmitters and their role in pathophysiology and treatment of depression. Introduction. Brain neurotransmitters are biological molecules responsible for signal transduction between the neurons. Mammalian brain neurotransmitters belong to the different types of biological molecules, such as amino acids (glutamate and ?-aminobutyric acid, or GABA), monoamines (serotonin (5-HT), norepinephrine (NE), dopamine (DA), and histamine (HA)), neuropeptides (?-endorphin, neurokinin, vasopressin, and oxytocin), or nucleotides (adenosine). Materials and Methods. The author analyzes research papers dedicated to neurotransmitters and their functions in mood regulation and published between 1953 and 2014. The paper focuses on evaluation of data on mechanisms of interactions between different neurotransmitters and their role in development and treatment of certain mental disorders. Results. It has been reported that different neurotransmitters, often belonging to the different types of biological molecules, interact on behavioral, functional, system and molecular levels. These interactions play an important role in pathophysiology of brain diseases, particularly, depression and stress and anxiety-related disorders. Conclusion. Literally all existing antidepressant drugs act on monoamine systems of the brain (5-HT, NE, and DA). Although the last-generation antidepressants and mood stabilizers demonstrated higher safety and efficacy, their therapeutic potential remains limited. The brain adenosine neurotransmission is also a potential target for the future antidepressant, mood stabilizing and antipsychotic drugs. However, these drugs may have severe side effects, for example, on cardiac activity. It is necessary to perform further research and clinical trials to find a solution to the existing difficulties.

References

1. Airaksinen A.J., Jablonowski J.A., van der Mey M., Barbieret A.J. Radiosynthesis and Biodistribution of a Histamine H3 Receptor Antagonist 4-[3-(4-Piperidin-1-yl-But-1-Ynyl)-[11C]Benzyl]-Morpholine: Evaluation of a Potential PET Ligand. Nucl Med Biol (England), 2006, vol. 33, pp. 801–810.
2. Airaksinen M.S., Panula P. The Histaminergic System in the Guinea Pig Central Nervous System: An Immunocytochemical Mapping Study Using an Antiserum Against Histamine. J Comp Neurol (United States), 1988, vol. 273, pp. 163–186.
3. Airaksinen M.S., Flugge G., Fuchs E., Panula P. Histaminergic System in the Tree Shrew Brain. J Comp Neurol (United States), 1989, vol. 286, pp. 289–310.
4. Allmark M.G., Lu F.C., Carmichael E., Lavallee A. Some Pharmacological Observations on Isoniazid and Iproniazid. Ammerical Reviews in Tuberculosis, 1953, vol. 68, pp. 199–206.
5. Bakker R.A., Timmerman H., Leurs R. Histamine Receptors: Specific Ligands, Receptor Biochemistry, and Signal Transduction. Clin Allergy Immunol (United States). 2002, vol. 17, pp. 27–64.
6. Blier P., Montigny C. Serotoninergic But Not Noradrenergic Neurons in Rat Central Nervous System Adapt to Long-Term Treatment with Monoamine Oxidase Inhibitors. Neuroscience (England), 1985, vol. 16, pp. 949–955.
7. Blier P., Montigny C.D., Azzaro A.J. Modification of Serotonergic and Noradrenergic Neurotransmissions by Repeated Administration of Monoamine Oxidase Inhibitors: Electrophysiological Studies in the Rat Central Nervous System. J Pharmacol Exp Ther (United States), 1986, vol. 237, pp. 987–994.
8. Brown R.E., Stevens D.R., Haas H.L. The Physiology of Brain Histamine. Prog Neurobiol (England), 2001, vol. 63, pp. 637–672.
9. Connelly W.M., Shenton F.C., Lethbridge N. The Histamine H4 Receptor is Functionally Expressed on Neurons in the Mammalian CNS. Br J Pharmacol (England), 2009, vol. 157, pp. 55–63.
10. Corrodi H., Fuxe K. The Effect of Imipramine on Central Monoamine Neurons. J Pharm Pharmacol (England), 1968, vol. 20, pp. 230–231.
11. Cremers T.I., Rea K., Bosker F.J., Wikstromet H.V. Augmentation of SSRI Effects on Serotonin by 5-HT2C Antagonists: Mechanistic Studies. Neuropsychopharmacology (United States), 2007, vol. 32, pp. 1550–1557.
12. Cremers T.I., Giorgetti M., Bosker F.J., Hogg S., Arnt J. Inactivation of 5-HT(2C) Receptors Potentiates Consequences of Serotonin Reuptake Blockade. Neuropsychopharmacology (United States), 2004, vol. 29, pp. 1782–1789.
13. Delay J., Buisson J.F. Psychic Action of Isoniazid in the Treatment of Depressive States. Journal of Clinical and Experimental Psychopathololy, 1958, vol. 19. pp. 51–55.
14. Delgado P.L., Miller H.L., Salomon R.M. Tryptophan-Depletion Challenge in Depressed Patients Treated with Desipramine or Fluoxetine: Implications for the Role of Serotonin in the Mechanism of Antidepressant Action. Biol Psychiatry (United States), 1999, vol. 46, pp. 212–220.
15. Dremencov E., Mansari M.E., Blier P. Distinct Electrophysiological Effect of Paliperidone and Risperidone on the Firing Activity of Rat Serotonin and Norepinephrine Neurons. Psychopharmacology (Germany), 2007, vol. 194, pp. 63–72.
16. Dremencov E. Aiming at New Targets for the Treatment of Affective Disorders: An introduction. Curr Drug Targets (Netherlands), 2009, vol. 10, pp. 1050–1051.
17. Dremencov E., Mansari M.E., Blier P. Effects of Sustained Serotonin Reuptake Inhibition on the Firing of Dopamine Neurons in the Rat Ventral Tegmental Area. J Psychiatry Neurosci (Canada), 2009, vol. 34, pp. 223–229.
18. Dremencov E., Mansari M.E,, Blier P. Brain Norepinephrine System as a Target for Antidepressant and Mood Stabilizing Medications. Curr Drug Targets (Netherlands), 2009, vol. 10, pp. 1061–1068.
19. Dremencov E., Mansari M.E., Blier P. Noradrenergic Augmentation of Escitalopram Response by Risperidone: Electrophysiologic Studies in the Rat Brain. Biol Psychiatry, 2007, vol. 61, pp. 671–678.
20. Dremencov E., Gur E., Lerer B., Newman M.E. Effects of Chronic Antidepressants and Electroconvulsive Shock on Serotonergic Neurotransmission in the Rat Hippocampus. Prog Neuropsychopharmacol Biol Psychiatry (England), 2003, vol. 27, pp. 729–739.
21. Dremencov E., Gur E., Lerer B., Newman M.E. Effects of Chronic Antidepressants and Electroconvulsive Shock on Serotonergic Neurotransmission in the Rat Hypothalamus. Prog Neuropsychopharmacol Biol Psychiatry (England), 2002, vol. 26, pp. 1029–1034.
22. Dremencov E., Gispan-Herman I., Rosenstein M., Mendelman A., Overstreet D.H., Zohar J., Yadid G. The Serotonin-Dopamine Interaction is Critical for Fast-Onset Action of Antidepressant Treatment: In Vivo Studies in an Animal Model of Depression. Prog Neuropsychopharmacol Biol Psychiatry (England), 2004, vol. 28, pp. 141–147.
23. Mansari E.M., Guiard B.P., Chernoloz O., Ghanbari R., Katz N., Blier P. Relevance of Norepinephrine-Dopamine Interactions in the Treatment of Major Depressive Disorder. CNS Neurosci Ther (England), 2010, vol. 16, p. 17.
24. Guiard B.P., Mansari M.E., Merali Z., Blier P. Functional Interaction Between Monoaminergic Neurons. Biol Psychiatry, 2007, vol. 61, pp. 125–125.
25. Guiard B.P., Mansari E.M., Merali Z., Blier P. Functional Interactions Between Dopamine, Serotonin and Norepinephrine Neurons: An In-Vivo Electrophysiological Study in Rats with Monoaminergic Lesions. Int J Neuropsychopharmacol (England), 2008, vol. 11, pp. 625–639.
26. Haas H.L., Sergeeva O.A., Selbach O. Histamine in the Nervous System. Physiol Rev (United States), 2008, vol. 88, pp. 1183–1241.
27. Hew R.W., Hodgkinson C.R., Hill S.J. Characterization of Histamine H3-Receptors in Guinea-Pig Ileum with H3-Selective Ligands. Br J Pharmacol (England), 1990, vol. 101, pp. 621–624.
28. Iwase M., Homma I., Shioda S., Nakai Y. Histamine Immunoreactive Neurons in the Brain Stem of the Rabbit. Brain Res Bull (United States), 1993, vol. 32, pp. 267–272.
29. Kandel E.R., Schwartz J.H., Jessell T.M. Principles of Neural Science. New York: McGraw-Hill, Health Professions Division, 2000.
30. Kawahara Y., Kawahara H., Kaneko F., Tanaka M. Long-Term Administration of Citalopram Reduces Basal and Stress-Induced Extracellular Noradrenaline Levels in Rat Brain. Psychopharmacology (Germany), 2007, vol. 194, pp. 73–81.
31. Kennedy S.H. A Review of Antidepressant Treatments Today. Eur Neuropsychopharmacol (Netherlands), 2006, vol. 5, pp. 619–623.
32. Leurs R., Blandina P., Tedford C., Timmerman H. Therapeutic Potential of Histamine H3 Receptor Agonists and Antagonists. Trends Pharmacol Sci (England), 1998, vol. 19, pp. 177–183.
33. Lin J.S., Hou Y., Sakai K., Jouvet M. Histaminergic Descending Inputs to the Mesopontine Tegmentum and Their Role in the Control of Cortical Activation and Wakefulness in the Cat. J Neurosci (United States), 1996, vol. 16, pp. 1523–1537.
34. Martinez-Mir M.I., Pollard H., Moreau J., Arrang J.M., Ruat M., Traiffort E., Schwartz J.C., Palacios J.M. Three Histamine Receptors (H1, H2 and H3) Visualized in the Brain of Human and Non-Human Primates. Brain Res (Netherlands), 1990, vol. 526, pp. 322–327.
35. Moret C., Briley M. Effect of Antidepressant Drugs on Monoamine Synthesis in Brain in Vivo. Neuropharmacology (England), 1992, vol. 31, pp. 679–684.
36. Panula P., Pirvola U., Auvinen S., Airaksinen M.S. Histamine-Immunoreactive Nerve Fibers in the Rat Brain. Neuroscience (England), 1989, vol. 28, pp. 585–610.
37. Pollard H., Moreau J., Arrang J.M., Schwartz J.C. A Detailed Autoradiographic Mapping of Histamine H3 Receptors in Rat Brain Areas. Neuroscience (England), 1993, vol. 52, pp. 169–189.
38. Ravindran L., Kennedy S.H. Are Antidepressants as Effective as Claimed? Yes, But... Can J Psychiatry (Canada), 2007, vol. 52, pp. 98–99.
39. Robot M. Isoniazid and Its Psychological Effects. Annual Medical Psychology (Paris), 1954, vol. 112, pp. 161–183.
40. Salzer H.M., Lurie M.L. Depressive States Treated with Isonicotinyl Hydrazide (Isoniazid); A Follow-Up Study. Ohio Medicine, 1955, vol. 51, pp. 437–441.
41. Schlicker E., Malinowska B., Kathmann M., Gothert M. Modulation of Neurotransmitter Release Via Histamine H3 Heteroreceptors. Fundam Clin Pharmacol (France), 1994, vol. 8, pp. 128–137.
42. Schlicker E., Kathmann M., Detzner M., Exner H.J., Gothert M. H3 Receptor-Mediated Inhibition of Noradrenaline Release: An Investigation into the Involvement of Ca2+ and K+ Ions, G Protein and Adenylate Cyclase. Naunyn Schmiedebergs Arch Pharmacol (Germany), 1994, vol. 350, pp. 34–41.
43. Vanhala A., Yamatodani A., Panula P. Distribution of Histamine-, 5-Hydroxytryptamine-, and Tyrosine Hydroxylase-Immunoreactive Neurons and Nerve Fibers in Developing Rat Brain. J Comp Neurol (United States), 1994, vol. 347, pp. 101–114.
44. Vollinga R.C., Koning J.P., Jansen F.P., Leurs R., Menge W.M., Timmerman H. A New Potent and Selective Histamine H3 Receptor Agonist, 4-(1H-Imidazol-4-Ylmethyl) Piperidine. J Med Chem (United States), 1994, vol. 37, pp. 332–333.

References on translit

Published
2016-06-01
How to Cite
Dremencov, E. (2016). THE ROLE OF INTERACTIONS BETWEEN BRAIN NEUROTRANSMITTERS IN PATHOPHYSIOLOGY AND TREATMENT OF AFFECTIVE DISORDERS. Human. Sport. Medicine, 16(2), 18-29. https://doi.org/10.14529/hsm160202
Section
Clinical and Experimental Medicine