Comparison of intrastriatal injections of quinolinic acid and 3-nitropropionic acid for use in animal models of Huntington's disease.

1. The present study compared the effects of acute intrastriatal administration of quinolinic acid (QA) and 3-nitropropionic acid (3-NP), two neurotoxins used in animal models of Huntington's disease (HD), on the following behavioral and histological measures: (1) open field activity levels; (2) performance on balance beam and grip strength tasks; (3) acquisition of a radial-arm-water-maze (RAWM) task; (4) size of striatum and lateral ventricles; (5) amount of cytochrome oxidase (CYO) labeling; and (6) counts of Nissl-stained neurons and NADPH-diaphorase-labeled neurons in the striatum. 2. Rats were given bilateral intrastriatal injections of either 200 nmol QA, 750 nmol 3-NP, or phosphate buffered saline (PBS) two weeks prior to behavioral testing and four weeks prior to histological processing. 3. The behavioral results indicated that both QA and 3-NP injections caused an increase in activity levels at two weeks postlesion, but only the QA rats showed hyperactivity at four weeks postlesion. Both QA and 3-NP rats showed significant impairment in the balance beam task, but only 3-NP rats differed significantly on the grip-strength task. Both toxins caused learning impairments in the RAWM task, with 3-NP rats being more severely impaired. 4. The neuroanatomical results indicated that both QA and 3-NP produced significant striatal atrophy and ventricular dilation, as well as a reduction in CYO staining and loss of Nissl-stained neurons, but only the 3-NP lesions created necrotic cavities in the striatum. However, the QA treatments resulted in significant loss of NADPH-diaphorase neurons in regions peripheral to the site of injection. 5. In general, these results suggest that QA treatments produce milder behavioral and neuroanatomical effects that mimic some of the earlier symptoms of HD, while 3-NP produced more severe effects which mimic both the later symptoms and the juvenile onset of HD.