Involvement of GABA neurons in allylnitrile-induced dyskinesia

Nitriles are a class of compounds with potential relevance to human health. Allylnitrile, one of nitriles, induces persistent behavioral abnormalities in mice. To explore what type of neuronal system is involved in these beha vioral abnormalities, five neuronal markers, gamma -aminobutyric acid (GABA ), tyrosine hydroxylase, serotonin, the serotonin transporter and choline a cetyltransferase were immunohistochemically examined within various brain s tructures in allylnitrile and vehicle-treated mice. Allylnitrile induced ch anges in the immunolabelling of GABA in the medial habenula, interpeduncula r nucleus, substantia nigra, dorsal raphe nucleus and median raphe nucleus; the amount of immunolabelling decreased in all of these brain structures e xcept the medial habenula at 2 days postdosing, and increased in all of the se structures at 14 days postdosing. Allylnitrile also induced changes in t he amount of immunolabelling of tyrosine hydroxylase in the arcuate nucleus , substantia nigra pars compacta, locus coeruleus and caudoventrolateral re ticular nucleus at either 2 or 14 days postdosing, depending on the structu res. No immunohistochemical change was seen for serotonin, serotonin transp orter and choline acetyltransferase. The present results suggest that the G ABAergic systems through the medial habenula-interpeduncular nucleus-ascend ing raphe nuclei relay and through the substantia nigra may be involved in allylnitrile-induced behavioral abnormalities. (C) 2000 Elsevier Science B. V. All rights reserved.