Chemical and anatomical changes in the striatum and substantia nigra following quinolinic acid lesions in the striatum of the rat: a detailed time course of the cellular and GABA(A) receptor changes

The pattern and time-course of cellular, neurochemical and receptor changes in the striatum and substantia nigra were investigated following unilatera l quinolinic acid lesions of the striatum in rats. The results showed that in the central region of the striatal lesion there was a major loss of Niss l staining of the small to medium sized cells within 2 h and a substantial loss of neuronal staining within 24 h after lesioning. Immunohistochemical studies showed a total loss of calbindin immunoreactivity, a known marker o f GABAergic striatal projection neurons, throughout the full extent of the quinolinic acid lesion within 24 h. Similarly, within 24 h, there was a tot al loss of somatostatin/neuroprptide Y cells in the centre of the lesion bu r in the periphery of the lesion these cells remained unaltered at all surv ival times. Striatal GABA, receptors remained unchanged in the lesion for 7 days, and then declined in density over the remainder of the time course. Glial fibrillary acidic protein immunoreactive astrocytes were present in t he periphery of the lesion at 7 days, occupied the full extent of the lesio n by 4 weeks, and remained elevated for up to 2 months. In the substantia n igra, following placement of a striatal quinolinic acid lesion, there was: a loss of substance P immunoreactivity within 24 h; a marked astrocytosis e vident from 1-4 weeks postlesion; and, a major increase in GABA(A) receptor s in the substantia nigra which occurred within 2 h postlesion and was sust ained for the remainder of the time course (15 months). This study shows th at following quinolinic acid lesions of the striatum there is a major loss of calbindin and somatostatin/neuropeptide Y immunoreactive cells in the st riatum within 24 h, and a marked increase in GABA, receptors in the substan tia nigra within 2 h. These findings are similar to the changes in the basa l ganglia in Huntington's disease and provide further evidence supporting t he use of the quinolinic acid lesioned rat as an animal model of Huntington 's disease. (C) 1999 Elsevier Science B.V. All rights reserved.