Histamine infusion induces a selective dopaminergic neuronal death along with an inflammatory reaction in rat substantia nigra

We have evaluated the effects of a direct infusion of histamine, as mediato r of inflammatory response, in substantia nigra, striatum, medial septum, a nd medial lemniscus. Injection of 100 and 250 nmol of histamine in substant ia nigra produced a selective damage in dopaminergic neurons evidenced by t he loss of tyrosine hydroxylase mRNA-expressing cells, tyrosine hydroxylase -immunolabeled-positive cell bodies, and dopamine and 3,4-dihydroxyphenylac etic acid levels. In parallel we found an acute inflammatory response manif ested by a loss of glial fibrillary acidic protein-immunolabeled astrocytes and, at precisely the same area, an activation of microglia. In the striat um, only high doses (500 nmol) produced an evident terminal degeneration. T he selective neurotoxicity of histamine for dopaminergic cells was demonstr ated by the unaltered transcription of glutamic acid decarboxylase mRNA in substantia nigra. Moreover, intraseptal injection of 100 nmol of histamine failed to alter the pattern of choline acetyltransferase mRNA-expressing ce lls. and intraparenchymal injection of histamine in medial lemniscus failed to alter the pattern of serotonin-immunolabeled cells. We conclude that th e substantia nigra is highly sensitive to histamine-derived neurotoxicity, where inflammatory processes mediated by histamine could be important in th e pathological changes that lead to dopaminergic neuronal damage after hist amine infusion.