Depletion of glutamate GluR2 receptor-containing neurons in the rat neostriatum by specific immunotoxin

In the present study, a novel GluR2 receptor-specific immunotoxin was produ ced. The immunotoxin was produced by conjugation of molecules of trichosant hin, a ribosome inactivating protein, with goat anti-mouse immunoglobulin m olecules. The secondary antibody was then combined with a commercially avai lable GluR2 specific primary antibody to form an immunotoxin. The immunotox ins were unilaterally injected either into the neostriatum or into the late ral ventricle of rats. After one week, ipsilateral turning movements were o bserved after apomorphine treatments in those animals injected by the stria tal route. In perfuse-fixed sections of the neostriatum, immunoreactivity f or GluR2 was found to decrease in the striatal-lesioned animals. Most of th e GluR2-immunoreactive perikarya in the neostriatum, the presumed medium sp iny neurons, were depleted. In addition, immunoreactivity for GluR2/3, GluR 5/6/7 and NMDAR1 was found to decrease to a different extent in the lesione d neostriatum. The number of GluR1-immunoreactive perikarya in the neostria tum, a group of striatal interneurons, was not affected by the GluR2 lesion . Ventricular administration of the GluR2 immunotoxin however, was found to be less potent. These results demonstrate for the first time that an indirect immunotoxin i s useful for immunolesioning. A difference in potency was also observed in different routes of administration. The depletion of GluR2-containing mediu m spiny neurons in the neostriatum may upset the balance of the output syst ems of the basal ganglia and has a profound effect in movement control of t he animals. (C) 2000 IBRO. Published by Elsevier Science Ltd.