Restraint-induced stress (RS) increases histamine concentration in the brain. There is no previous report regarding the role of histamine receptors in immunomodulatory effect of RS. In the present study the role of brain histamine receptors on reduction of humoral and cellular immune function induced by RS was evaluated. For this purpose male Wistar rats (200-250 g) were immunized with sheep red blood cells (SRBCs). The results showed that RS reduced the humoral and cell-mediated immunity in immunized rats (p<0.01). Similarly, ICV injection of histamine (150 µg/rat) without stress reduced significantly humoral and cellular immune function (p<0.01). Pretreatment with chlorpheniramine (50 µg/rat) reduced the inhibitory effect of RS. In addition, histamine (150 µg/rat) could inhibit the effect of chlorpheniramine if injected simultaneously. Ranitidine (10 µg/rat) had no significant effect. ICV injection of lower doses of R-α-methyl histamine reduced the effect of RS on immune function, but the effect of RS on immunity increased at higher doses (10 µg/rat) of the drug. These results indicated that histamine has a central role in RS-induced immunosuppression through brain's H1 receptors. Furthermore H3 histamine receptors induce a dose-dependent bi-directional effect, which may be due to the role of this receptor in non- histaminic nervous system.

Keywords: Restraint stress; Histamine; Immune system; Central histamine receptors

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