Dopamine D1- and D2-Receptors in Immunostimulation under Activation of Mu-Opioid Receptors in Mice with Different Psychoemotional States

DOI: 10.4236/pp.2014.51008   PDF   HTML   XML   3,939 Downloads   5,139 Views  


The purpose of the present study was to analyze the effect of activation of mu-opioid receptors (mu-OR) on the immune response under blockade of postsynaptic D1-and D2-receptors in mice of the C57BL/6J strain displaying either aggressive or depressive-like behaviors in the social conflict model. It is shown that activation of activation of mu-OR with a highly selective agonist DAGO (100 μg/kg) increased significantly IgM-immune response not only in C57BL/6J mice with an unchanged psychoemotional state but also in mice displaying aggressive or depressive-like behaviors in the social stress model (10 days of agonistic confrontations). Selective blockade of DA receptors of the D1-type with SCH-23390 (1.0 mg/kg with DAGO administration) caused a more pronounced elevation of IgM-immune response than DAGO alone while DAGO effect was completely blocked by prior administration of D2-receptor antagonist haloperidol (1.0 mg/kg). At the same time, both SCH-23390 and haloperidol prevented the immune response increase induced by DAGO injection in mice engaged in aggressive or depressive-like behaviors. Thus, in animals not subjected to social stress DAGO-induced immunostimulation is provided only by D2-receptors, whereas in animals with altered psychoemotional state mu-opioid immunostimulation is mediated by both types of DA receptors—D1 and D2. These data provide evidence for different impacts of the main subtypes of DA receptors in the mediation of immunomodulating effects of mu-opioid system under normal and stressful conditions.

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M. Cheido, G. Idova and E. Alperina, "Dopamine D1- and D2-Receptors in Immunostimulation under Activation of Mu-Opioid Receptors in Mice with Different Psychoemotional States," Pharmacology & Pharmacy, Vol. 5 No. 1, 2014, pp. 43-48. doi: 10.4236/pp.2014.51008.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] M. A. Cheido and G. V. Idova, “The Effect of Opioid Peptides on the Immunomodulation Process,” Rossijiskii Fiziologicheskiji Zhurnal imeni I. M. Sechenova, Vol. 84, No. 4, 1998, pp. 385-390.
[2] C. J. Nelson, G. M. Schneider and D. T. Lysle, “Involvement of Central Mubut not Deltaor Kappa-Opioid Receptors in Immunomodulation,” Brain, Behavior, and Immunity, Vol. 14, No. 3, 2000, pp. 170-184.
[3] R. T. Rahim, J. J. Meissler Jr., A. Cowan, T. J. Rogerts, E. B. Geller, J. Gaughan, M. W. Adler and T. K. Eisenstein, “Administration of Mu-, Kappaor Delta2-Receptor Agonists via Osmotic Minipumps Suppresses Murine Splenic Antibody Responses,” International Immunopharmacology, Vol. 1, No. 11, 2001, pp. 2001-2009.
[4] L. Devoino, M. Cheido, E. Alperina and G. Idova, “Evidence for a Role of Dopaminergic Mechanisms in the Immunostimulating Effect of μ-Opioid Receptor Agonist DAGO,” International Journal of Neuroscience, Vol. 113, No. 10, 2003, pp. 1381-1394.
[5] T. B. Saurer, K. A. Carrigan, S. G. Ijames and D. T. Lysle, “Suppression of Natural Killer Cell Activity by Morphine Is Mediated by the Nucleus Accumbens Shell,” Journal of Neuroimmunology, Vol. 173, No. 1, 2006, pp. 3-11.
[6] M. A. Cheido and G. V. Idova, “Dopaminergic Mechanisms in Immunostimulating Effect of μ-Opioid Receptors,” Bulletin of Experimental Biology and Medicine, No. 4, 1996, pp. 373-375.
[7] M. A. Cheido and G. V. Idova, “The Differential Contribution of Dopamine D(1) and D(2) Receptors to MuOpioidergic Immunomodulation,” Neuroscience and Behavioral Physiology, Vol. 37, No. 7, 2007, pp. 721-724.
[8] M. A. Cheido and G. V. Idova, “Mu-Opioidergic Immunomodulation: The Neurochemical Basis,” Uspehi Fiziologicheskich Nauk, Vol. 40, No. 2, 2009, pp. 12-25.
[9] G. V. Idova, E. L. Alperina and M. A. Cheido, “Contribution of Brain Dopamine, Serotonin and Opioid Receptors in the Mechanisms of Neuroimmunomodulation: Evidence from Pharmacological Analysis,” International Immunopharmacology, Vol. 12, No. 4, 2012, pp. 618-625.
[10] L. Devoino, E. Alperina, O. Galkina and R. Ilyutchenok, “Involvement of Brain Dopaminergic Structures in Neuroimmunomodulation,” International Journal of Neuroscience, Vol. 91, No. 3-4, 1997, pp. 213-228.
[11] C. Ulens, M. Van Boven, P. Daenens and J. Tytgat, “Interaction of p-Fluorofentanyl on Cloned Human Opioid Receptors and Exploration of the Role of Trp-318 and His-319 in μ-Opioid Receptor Selectivity,” Journal of Pharmacology and Experimental Therapeutics, Vol. 294, No. 3, 2000, pp. 1024-1033.
[12] C. Missale, S. R. Nash, S. W. Robinson, M. Jaber and M. G. Caron, “Dopamine Receptors: From Structure to Function,” Physiological Reviews, Vol. 78, No. 1, 1998, pp. 189-225.
[13] A. Mansour, C. A. Fox, S. Burke, H. Akil and S. Watson, “Immunohistochemical Localization of the Cloned MuOpioid Receptor in the Rat CNS,” Journal of Chemical Neuroanatomy, Vol. 8, No. 4, 1995, pp. 283-305.
[14] Y. Q. Ding, T. Kaneko, S. Nomura and N. Mizuno, “Immunohistochemical Localization of Mu-Opioid Receptors in the Central Nervous System of the Rat,” Journal of Comparative Neurology, Vol. 367, No. 3, 1996, pp. 375-402.<375::AID-CNE5>3.0.CO;2-2
[15] L. M. Ambrose, E. M. Unterwald and E. J. Van Bockstaele, “Ultrastructural Evidence for Co-Localization of Dopamine D2 and μ-Opioid Receptors in the Rat Dorsolateral Striatum,” The Anatomical Record Part A: Discoveries in Molecular, Cellular, and Evolutionary Biology, Vol. 279A, No. 1, 2004, pp. 583-591.
[16] R. Ader, “On the Development of Psychoneuroimmunology,” European Journal of Pharmacology, Vol. 405, No. 1-3, 2000, pp. 167-176.
[17] L. V. Devoino, G. V. Idova and E. L. Alperina, “Psychoneuroimmunomodulation: Behavior and Immunity. A Role for ‘The Neuromediator Pattern of the Brain’,” Novosibirsk: Nauka, 2009.
[18] E. Gomez-Lazaro, A. Arregi, G. Beitia, O. Vegas, A. Azpiroz and L. Garmendia, “Individual Differences in Chronically Defeated Male Mice: Behavioral, Endocrine, Immune, and Neurotrophic Changes as Markers of Vulnerability to the Effects of Stress,” Stress, Vol. 14, No. 5, 2011, pp. 537-548.
[19] A. R. Prossin, A. E. Koch, P. L. Campbell, M. G. Mclnnis, S. S. Zalcman and J. K. Zubieta, “Association of Plasma Interleukin-18 Levels with Emotion Regulation and μOpioid Neurotransmitter Function in Major Depression and Healthy Volunteers,” Biological Psychiatry, Vol. 69, No. 8, 2011, pp. 808-812.
[20] D. F. Avgustinovich, O. V. Alekseenko, I. V. Bakshtanovkaia, L. A. Koriakina, T. V. Lipina, M. V. Tenditnik, N. P. Bondar, I. L. Kovalenko and N. N. Kudriavtseva, “Dynamic Changes of Brain Serotonergic and Dopaminergic Activities during Development of Anxious Depression: Experimental Study,” Uspehi Fiziologicheskich Nauk, Vol. 35, No. 4, 2004, pp. 19-40.
[21] M. A. Cheido and G. V. Idova, “Immune Response of Submissive and Aggressive Mice under Conditions of Opioid Receptor Activation,” Bulletin of Experimental Biology and Medicine, Vol. 148, No. 6, 2009, pp. 886-888.
[22] N. P. Bondar, “Effect of Mu-and Kappa-Opioid Receptor Antagonists on Aggressiveness of Male Mice with Repeated Experience of Aggression,” Rossijiskii Fiziologicheskiji Zhurnal imeni I. M. Sechenova, Vol. 98, No. 6, 2012, pp. 681-692.
[23] N. N. Kudryavtseva, “А Sensory Contact Model for the Study of Aggressive and Submissive Behavior in Male Mice,” Aggressive Behavior, Vol. 17, No. 5, 1991, pp. 285-291.
[24] A. J. Cunningham, “A Method of Increased Sensitivity for Detecting Single Antibody Forming Cells,” Nature, Vol. 207, 1965, pp. 1106-1107.
[25] J. Kowalski, “Immunomodulatory Action of Class Mu-, Deltaand Kappa-Opioid Receptor Agonists in Mice,” Neuropeptides, Vol. 32, No. 4, 1998, pp. 301-306.
[26] M. A. Cheido and M. M. Gevorgyan, “Peculiarities of the Distribution of Cellular Subpopulations in the Spleen and Peripheral Blood of CBA Mice under Conditions of Activation of the Muand Delta-Opioid Systems,” Immunology, No. 5, 2011, pp. 886-887.
[27] S. V. Gein, T. A. Baeva, V. O. Nebogatikov and S. P. Tendryakova, “β-Endorphin Effects on Antibody Production, Proliferation, and Secretion of Th1/Th2 Cytokines in Vivo,” Bulletin of Experimental Biology and Medicine, Vol. 152, No. 5, 2012, pp. 595-599.
[28] S. Ito, T. Mori and T. Sawaguchi, “Differential Effects of Micro-Opioid, Delta-Opioid and Kappa-Opioid Receptor Agonists on Dopamine Receptor Agonist-Induced Climbing Behavior in Mice,” Behavioural Pharmacology, Vol. 17, No. 8, 2006, pp. 691-701.
[29] E. G. Guy, E. Choi and W. E. Pratt, “Nucleus Accumbens Dopamine and Mu-Opioid Receptors Modulate the Reinstatement of Food-Seeking Behavior by Food-Associated Cues,” Behavioural Brain Research, Vol. 219, No. 2, 2011, pp. 265-272.
[30] N. N. Kudriavtseva, T. G. Amstislavskaia, D. F. Avgustinovich, I. V. Bakshtanovskaia, T. V. Lipina and O. V. Gorbach, “The Effect of the Repeated Experience of Victories and Defeats in Social Conflicts on the Function of the Brain Serotoninergic System in Male Mice,” Zhurnal Vyssheji Nervnoji Deiatel’nosti imeni I. P. Pavlova, Vol. 46, No. 6, 1996, pp. 1088-1096.
[31] L. V. Devoino, E. L. Al’perina, E. Podgornaia, O. V. Poliakov, G. V. Idova and RIu. Il’iuchenok, “Involvement of Dopaminergic Systems in the Functional Specialization of Brain Areas during Formation of Aggressive and Submissive Behavior in Mice,” Zhurnal Vyssheji Nervnoji Deiatel’nosti imeni I. P. Pavlova, Vol. 51, No. 2, 2001, pp. 197-205.
[32] L. Devoino, E. Alperina, E. Podgornaja, R. Ilyutchenok, G. Idova and O. Poljakov, “Regional Changes of Brain Serotonin and Its Metabolite 5-Hydroxyindolacetic Acid and Development of Immunosuppression in Submissive Mice,” International Journal of Neuroscience, Vol. 114, No. 9, 2004, pp. 1049-1062.
[33] L. Devoino, E. Alperina and T. Pavina, “Immunological Consequences of the Reversal of Social Status in C57BL/ 6J Mice,” Brain, Behavior, and Immunity, Vol. 17, No. 1, 2003, pp. 28-34.
[34] L. H. Shen, M. H. Liao and Y. C. Tseng, “Recent Advances in Imaging of Dopaminergic Neurons for Evaluation of Neuropsychiatric Disorders,” Journal of Biomedicine and Biotechnology, Vol. 2012, 2012, pp. 259-349.
[35] E. Scarr, T. T. Money, G. Pavey, J. Neo and B. Dean, “Mu Opioid Receptor Availability in People with Psychiatric Disorders Who Died by Suicide: A Case Control Study,” BMC Psychiatry, Vol. 12, 2012, pp. 126-137.
[36] N. Müller and M. J. Schwarz, “Immune System and Schizophrenia,” Current Immunology Review, Vol. 6, No. 3, 2010, pp. 213-220.
[37] J. Blume, S. D. Douglas and D. L. Evans, “Immune Suppression and Immune Activation in Depression,” Brain, Behavior, and Immunity, Vol. 25, No. 2, 2011, pp. 221-229.

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