Simultaneous Intrastriatal 6-Hydroxydopamine and Quinolinic Acid Injection: A Model of Early-Stage Striatonigral Degeneration

Imad Ghorayeb, Zoe Puschban, Pierre O. Fernagut, Christoph Scherfler, Richard Rouland, Gregor K. Wenning, François Tison
Experimental Neurology. 2001-01-01; 167(1): 133-147
DOI: 10.1006/exnr.2000.7535

Ghorayeb I(1), Puschban Z, Fernagut PO, Scherfler C, Rouland R, Wenning GK,
Tison F.

Author information:
(1)Laboratoire de Neurophysiologie, CNRS-UMR 5543, Université Victor Segalen
Bordeaux 2, Bordeaux Cedex, 33076, France.

Animal models reproducing early stages of striatonigral degeneration (SND), the
core pathology underlying parkinsonism in multiple system atrophy, are lacking.
We have developed a new model of early-stage SND by using a simultaneous
unilateral administration of quinolinic acid (QA) and 6-hydroxydopamine (6-OHDA)
into the putaminal equivalent of the rat striatum. Spontaneous and drug-induced
behavior, thigmotactic scanning, paw reaching deficits, and histopathology were
studied in rat groups: group 1 (control), group 2 (QA), group 3 (6-OHDA), and
group 4 (QA + 6-OHDA). The double toxin administration resulted in reduction of
the spontaneous and the amphetamine-induced ipsiversive bias in the 6-OHDA group
and in a reduction of the apomorphine-induced ipsiversive rotations in the QA
group. Simultaneous QA and 6-OHDA also reduced the thigmotactic bias observed in
the 6-OHDA rats. Combined toxin elicited a nonsignificant contralateral deficit
in paw reaching but a significant deficit on the ipsilateral side.
Histopathology revealed a significant reduction of the lesioned striatal surface
(-27%) with neuronal loss and increased astrogliosis in group 4 compared to
group 2, consistent with an exacerbation of QA toxicity by additional 6-OHDA. By
contrast, the mean loss of the TH-positive neurons in the ipsilateral substantia
nigra pars compacta (SNc) of group 4 was less marked (-15%) than in the 6-OHDA
group (-36%), indicating a possible protective action of intrastriatal QA upon
6-OHDA retrograde SNc degeneration. This study shows that a combined unilateral
intrastriatal administration of QA and 6-OHDA may serve as a model of early
stage SND which is more suitable for early therapeutic interventions.