Changes in histamine in the rat striatum following local injection of kainic acid

The influence of local administration of kainic acid on the metabolism of histamine in the striatum of the rat has been investigated. Intrastriatal injection of kainic acid (1 μg) resulted in a more than 100% increase of the striatal content of histamine, which persisted from two days after the lesion up to ten weeks. Using two independent methods this accumulation of histamine has been found to be associated with a neuronal compartment of the striatum: (a) the concentration of histamine in synaptosomes prepared from kainic acid lesioned striatum was higher than in synaptosomes derived from the untreated (contralateral) striatum; (b) electrolytic lesions of the medial forebrain bundle, in animals whose striatum had been lesioned with kainic acid, abolished the increase in histamine levels induced by the neurotoxin. Since the rate of disappearance of histamine from the tissue after inhibition of its synthesis by α-fluoromethylhistidine (20 mg/kg, i.p.) was reduced in the lesioned striatum, the kainic acid induced increase in striatal histamine level may be due to a decrease of histamine turnover.Specific binding of [³H]histamine and [³H]cimetidine was measured in the lesioned striatum, revealing a 40% and 20% decrease in binding sites, respectively, when compared with the untreated striatum; the affinity for either ligand was not changed in the lesioned tissue.The data demonstrate considerable neurochemical changes involving the neuronal histamine system in the striatum after destroying the interneurons and output neurons of this region with the convulsive neurotoxin kainic acid.