RT Journal Article
SR Electronic
T1 Systemic approaches to modifying quinolinic acid striatal lesions in rats
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 3901
OP 3908
DO 10.1523/JNEUROSCI.08-10-03901.1988
VO 8
IS 10
A1 MF Beal
A1 NW Kowall
A1 KJ Swartz
A1 RJ Ferrante
A1 JB Martin
YR 1988
UL http://www.jneurosci.org/content/8/10/3901.abstract
AB Quinolinic acid (QA) is an endogenous excitotoxin present in mammalian brain that reproduces many of the histologic and neurochemical features of Huntington's disease (HD). In the present study we have examined the ability of a variety of systemically administered compounds to modify striatal QA neurotoxicity. Lesions were assessed by measurements of the intrinsic striatal neurotransmitters substance P, somatostatin, neuropeptide Y, and GABA. Histologic examination was performed with Nissl stains. The antioxidants ascorbic acid, beta-carotene, and alpha- tocopherol administered s.c. for 3 d prior to striatal QA lesions had no significant effect. Other drugs were administered i.p. 1/2 hr prior to QA striatal lesions. The following were ineffective in blocking QA excitotoxicity: allopurinol, 50 and 100 mg/kg; ketamine, 75 mg/kg; nimodipine, 2.4, and 10 mg/kg; baclofen, 10 mg/kg; 2-amino-5- phosphonovalerate, 50 mg/kg; and 2-amino-7-phosphonoheptanoate, 50 mg/kg. Oral taurine administration for 4 weeks resulted in significantly increased levels of brain taurine but had no significant effect in blocking QA neurotoxicity. Systemic administration of the noncompetitive N-methyl-D-aspartate (NMDA) antagonist MK-801 resulted in a dose-responsive protection against QA toxicity, with complete block at a dose of 4 mg/kg. If the pathogenesis of HD involves QA or another excitotoxin acting at the NMDA receptor, it is possible that MK- 801 could retard the degenerative process.