INTRASTRIATAL QUINOLINIC ACID INJECTIONS PROTECT AGAINST 6-HYDROXYDOPAMINE INDUCED LESIONS OF THE DOPAMINERGIC NIGROSTRIATAL SYSTEM

We tested the effect of intrastriatal quinolinic acid (QA) injections 2 weeks before subsequent intrastriatal injections of 6-hydroxydopamin e (6-OHDA). Levels of DA and its metabolites were measured 2 days and 21 days after lesioning the dopaminergic nigrostriatal system with 6-O HDA. Intrastriatal 6-OHDA injections in the absence of prior treatment of QA significantly decreased dopamine (DA) and its metabolite levels in striatum but not in substantia nigra at day 2, and in striatum and substantia nigra at day 21, a clear indication of a time-dependent re trograde axonal degeneration of substantia nigra cell bodies. Intrastr iatal QA injections 2 weeks before subsequent intrastriatal injection of 6-OHDA partially prevented the 6-OHDA-depleting effect on DA and it s metabolite levels in both striatum and substantia nigra 21 days afte r 6-OHDA injection. However, no statistically significant differences were found between QA + 6-OHDA- and B-OHDA-treated animals at day 2. O ur results suggest that intrastriatal QA injections partially prevent the naturally-occurring retrograde axonal degeneration of substantia n igra cell bodies caused by 6-OHDA, and illustrate a target-derived int eraction between dopaminergic nerve endings and cell bodies. We sugges t that the protective effect found in the QA-injected animals against the neurotoxic action of 6-OHDA is mediated by neurotrophic agents rel eased by activated astroglia.