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 behavioral abnormalities, five neuronal markers, gamma-aminobutyric acid (GABA), tyrosine hydroxylase, serotonin, the serotonin transporter and choline acetyltransferase were immunohistochemically examined within various brain structures in allylnitrile and vehicle-treated mice. Allylnitrile induced changes in the immunolabelling of GABA in the medial habenula, interpeduncular nucleus, substantia nigra, dorsal raphe nucleus and median raphe nucleus; the amount of immunolabelling decreased in all of these brain structures except the medial habenula at 2 days postdosing, and increased in all of these structures at 14 days postdosing. Allylnitrile also induced changes in the amount of immunolabelling of tyrosine hydroxylase in the arcuate nucleus, substantia nigra pars compacta, locus coeruleus and caudoventrolateral reticular nucleus at either 2 or 14 days postdosing, depending on the structures. No immunohistochemical change was seen for serotonin, serotonin transporter and choline acetyltransferase. The present results suggest that the GABAergic systems through the medial habenula-interpeduncular nucleus-ascending raphe nuclei relay and through the substantia nigra may be involved in allylnitrile-induced behavioral abnormalities.