Recombinant IL-1β induces striatal dopamine depletion in aged rats: Involvement of histamine H₁ receptors

Aging, the strongest risk factor for Parkinson's disease (PD), is associated with brain neuroinflammation. In parkinsonian brain, this inflammation manifests in elevated levels of interleukin-1β (IL-1β). The pathogenic significance of this factor is unclear. The presented study was aimed to examine the effect of IL-1β analogue, rat recombinant IL-1β (rrIL-1β), on striatal dopamine metabolism in aged rats; in parallel, cataleptogenic action of rrIL-1β was determined. Given the ability of IL-1β to induce histamine release from histaminergic fibers, the involvement of histamine H₁, H₂, H₃, and H₄ receptors in the rrIL-1β effects was evaluated. The male Wistar rats of 530-570 days of age were used in all experiments. The experimental groups consisted of 6 animals. The striatal levels of dopamine (DA), 3, 4 -dihydroxyphenylacetic acid (DOPAC), and tyrosine hydroxylase (TH) were determined using HPLC and ELISA; catalepsy was assessed by bar test. Daily i.c.v. administration of rrIL-1β for 14 days at 3.0 ng caused significant decrease in DA, DOPAC, and TH levels in the dorsal striatum; these neurochemical changes were accompanied with the development of catalepsy. The observed rrIL-1β effects were reversed by H₁ antagonist mepyramine whereas H₂ and H₃/H₄ antagonists ranitidine and thioperamide were ineffective. The presented results provide novel insight into functioning of the nigrostriatal pathway in aged rats. Apparently, there exists a certain IL-1β-histamine mechanism exerting depletion of dopamine in the dorsal striatum and initiating catalepsy; the mechanism is mediated by H₁ receptors. Our data suggest that the IL-1β-histamine interaction might contribute to the PD development, and be potential target for the treatment of parkinsonism.