Immunolesioning of glutamate receptor GluR1-containing neurons in the rat neostriatum using a novel immunotoxin

1. To investigate the potency of a novel immunotoxin that is specific for g lutamate receptor GluR1, a subunit of the alpha-amino-3-hydroxy-5-methyl-4- isoxazole(AMPA)-type receptor channel, immunolesioning was performed. 2. A ribosome-inactivating protein, trichosanthin (TCS), was isolated and c onjugated to the goat anti-rabbit IgG antibody molecule. The anti-rabbit an tibody-TCS complex was preincubated with GluR1-specific rabbit antibody to produce a GluR1-specific immunotoxin. The immunotoxin was unilaterally admi nistered into either the neostriatum or the lateral ventricle of rats. 3. Immunoreactivity for GluR1 or GluR4 was revealed in perfuse-fixed sectio ns of the neostriatum obtained from the lesioned and control animals by imm unocytochemistry. After ventricular or striatal injections of the immunotox in, depletions of GluR1-immunoreactive neurons, the presumed GABAergic inte rneurons in the neostriatum, were found. Depletions of GluR4-immunoreactive perikarya, the presumed same subpopulation of striatal interneurons, were also found. In addition, no change in the pattern of distribution of immuno reactivity for GluR2 or glial fibrillary acidic protein was found in the le sioned neostriatum. These results indicate that the novel GluR1 immunotoxin is potent and specific. 4. In addition, striatal application of the immunotoxin caused a greater de pletion in the number of GluR1-immunoreactive neurons. The present results also indicate that the route of immunotoxin application may be important in producing specific lesions.