Simultaneous intrastriatal 6-hydroxydopamine and quinolinic acid injection: a model of early-stage striatonigral degeneration.

Abstract

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.

• Authors: I Ghorayeb, Z Puschban, P O Fernagut, C Scherfler, R Rouland, G K Wenning, F Tison
• Journal: Experimental neurology (Exp Neurol) Vol. 167 Issue 1 Pg. 133-47 (Jan 2001) ISSN: 0014-4886 [Print] United States
• PMID: 11161601 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Oxidopamine
• Tyrosine 3-Monooxygenase
• Quinolinic Acid

Topics

• Animals
• Behavior, Animal (drug effects)
• Cell Count
• Corpus Striatum (drug effects, pathology, physiopathology)
• Disease Models, Animal
• Forelimb
• Male
• Microinjections
• Motor Activity (drug effects)
• Motor Skills (drug effects)
• Multiple System Atrophy (pathology, physiopathology)
• Neurodegenerative Diseases (chemically induced, pathology, physiopathology)
• Neurons (enzymology, pathology)
• Oxidopamine (administration & dosage)
• Quinolinic Acid (administration & dosage)
• Rats
• Rats, Wistar
• Reaction Time (drug effects)
• Substantia Nigra (drug effects, pathology, physiopathology)
• Touch (drug effects)
• Tyrosine 3-Monooxygenase (metabolism)