Evidence for a role of dopaminergic mechanisms in the immunostimulating effect of mu-opioid receptor agonist DAGO

The present study demonstrates that: (1) activation of micro -opioid receptors by systemic administration of a highly selective agonist DAGO (100 microg/kg) results in a significant increase in the number of plaque- and rosette-forming cells in the spleen of CBA mice as well as Wistar rats on the 5th day following sheep red blood cells (5 x 10(8)) immunization, (2) the immunostimulatory effect of DAGO is mediated by central mechanisms including the hypothalamus-hypophysis complex; (3) the postsynaptic dopamine (DA) receptors of D2 type are involved in the DAGO-induced immunostimulation since the combined treatment of animals with haloperidol (2 mg/kg), a blocker of DA D2 receptors, and DAGO abolished this effect; (4) the nuclei caudatus and accumbens of the nigrostriatal and mesolimbic DAergic systems, respectively, are implicated in the immune response stimulation caused by DAGO.     

Involvement of the Nucleus Accumbens in Stimulation of the Immune Response in Rats after Activation of Opioid μ Receptors with DAGO

The involvement of the nucleus accumbens in neuroimmunostimulation was demonstrated during activation of opioid receptors with the selective agonist DAGO (100 g/kg); single doses of this agent to sham-operated (control) Wistar rats induced significant increases in the numbers of direct IgM antibody-forming and total rosette-forming cells after immunization with sheep erythrocytes. Bilateral electrolytic lesioning of the nucleus accumbens in rats led to sharp decreases in the intensity of immune responses; there was no immunostimulation after administration of DAGO to these animals. These data provide evidence for the involvement of the nucleus accumbens in the process of immunomodulation and for the importance of opioid receptors in the nucleus accumbens in the stimulation of immunogenesis.     

Involvement of the Rat Caudate Nucleus in the Immunostimulatory Effect of Dago

The involvement of the caudate nucleus, i.e., the terminal zone of the nigrostriatal dopaminergic system, in neuroimmunostimulation during the activation of opioid receptors by the highly specific agonist DAGO. Single doses of DAGO (100 g/kg) in sham-operated control Wistar rats induced significant increases in the numbers of direct IgM-antibody-forming and total rosette-forming cells at the peak of the immune response after immunization with sheet red blood cells. The experiments showed that bilateral electrolytic lesioning of the caudate nucleus in rats suppressed the immune response, demonstrating its involvement in neuroimmunomodulation. Since the effect of immunostimulation induced by DAGO disappeared when given to animals with caudate nucleus lesions, it was concluded that this structure is involved in activatory immunogenesis via opioid mechanisms.     

Stimulation of the Immune Response During Activation of the Dopaminergic System in Mice with Opposite Types of Behavior

Studies reported here demonstrated that activation of the dopaminergic system induces increases in the immune response regardless of the type of behavior in mice (line CBA), i.e., in aggressive mice, submissive mice, and mice lacking experience of victory or defeat (controls). Changes in the activity of the dopaminergic system were induced with SKF-38393, a selective agonist of dopamine D1 receptors, and with p-chlorophenylalanine (PCPA), which we have previously shown to activate D2 receptors. In the aggressive form of behavior, which was characterized by strong (compared with controls) immune responses, SKF-38393 and PCPA led to further increases in the immune response. In submissive mice, activation of the dopaminergic system altered the nature of the immune response, with immunostimulation, as in aggression. It is suggested that activation of the dopaminergic system in conditions of defined psychoemotional status fixed by acquisition of opposite types of behavior, induces the formation of a new neurochemical pattern--the dopaminergic set--which led to changes in the nature and intensity of the immune response.     

Changes in levels of dopamine and its metabolites in brain structures and immunocompetent organs during formation of the immune response

Laboratory of Mechanisms of Memory Regulation and Laboratory of Mechanisms of Neurochemical Modulation Institute of Physiology, Siberian Branch, Academy of Medical Sciences of the USSR, Novosibirsk. (Presented by Academician of the Academy of Medical Sciences of the USSR Yu. P. Nikitin.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 110, No. 7, pp. 66–68, July, 1990.     

Serotonin and 5-hydroxyindoleacetic acid levels in the brain and immunocompetent organs after immunization

Laboratory of Mechanisms of Memory Regulation and Laboratory of Mechanisms of Neurochemical Modulation Institute of Physiology, Siberian Branch, Academy of Medical Science of the USSR, Novosibirsk. (Presented by Academician of the Academy of Medical Sciences of the USSR Yu. P. Nikitin.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 110, No. 8, pp. 178–180, August, 1990.     

Changed count of CD4+ T-lymphocytes in the bone marrow of aggressive CBA mice

Enhanced immune response of aggressive CBA mice after 10 daily confrontations in sensory contact on day 4 after immunization with sheep red blood cells (5×10⁸) is paralleled by an increase in the count of CD4⁺ T-cells in the bone marrow. Aggressive behavior, weight of the spleen, and count of CD4⁺ T-helpers in the bone marrow (which is increased only in aggressors with a history of at least 3 victories) are correlated. The effect of aggressive behavior on immunity can be caused by changes of the neurochemical status of the brain and determined by an increase in the CD4⁺ T-helper count. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 124, No. 11, pp. 544–546, November, 1997     

Brain Content of 5-Hydroxytryptamine and 5-Hydroxyindoleacetic Acid and Immune Response in Aggressive C57Bl/6J Mice

Catabolism of 5-hydroxytryptamine in the midbrain raphe nuclei of aggressive C57Bl/6J mice increased after 10 and 20 days of confrontations. Both catabolism and concentration of 5-hydroxytryptamine increased in the dopaminergic nuclei A11, A10, A9, and in the amigdala. The level of 5-hydroxyindoleacetic acid in the A9 and raphe nuclei decreased after 20 days of confrontations, which coincided with manifestation of the immune response.