Abstract
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.
Highlights
At present there is strong evidence for the involvement of central mu-opioid system in immunomodulation [1,2,3,4,5]
Our previous data have shown that the nigrostriatal and mesolimbic DAergic structures are playing an important role in immunostimulation [10] induced by a highly selective [11] agonist of mu-opioid receptors DAGO [4]
Activation of mu-opioid receptors (mu-OR) with a highly selective agonist DAGO (100 μg/kg) produced a significant increase of IgM-immune response (F(1,12) = 79.99; p < 0.001) in C57BL/6J mice having no experience of social encounters when compared to the vehicle-injected group (Figure 1)
Summary
At present there is strong evidence for the involvement of central mu-opioid system in immunomodulation [1,2,3,4,5]. Our previous data have shown that the nigrostriatal (nucleus caudatus) and mesolimbic (nucleus accumbens) DAergic structures are playing an important role in immunostimulation [10] induced by a highly selective [11] agonist of mu-opioid receptors (mu-OR) DAGO [4]. These brain structures have been found to contain significantly high amounts of DA D1- and D2receptors [12] and of mu-OR [13]. Mu-opioid and DA mechanisms have been found to be implicated in the reg-
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