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A rat model of striatonigral degeneration generated by simultaneous injection of 6-hydroxydopamine into the medial forebrain bundle and quinolinic acid into the striatum.

Abstract
A double toxin-double lesion strategy is well-known to generate a rat model of striatonigral degeneration (SND) such as multiple system atrophy-parkinsonian type. However, with this model it is difficult to distinguish SND from Parkinson's disease (PD). In this study, we propose a new rat model of SND, which is generated by simultaneous injection of 6-hydroxydopamine into the medial forebrain bundle and quinolinic acid into the striatum. Stepping tests performed 30 min after intraperitoneal L-dopa administration at 6 weeks post-surgery revealed an L-dopa response in the PD group but not the SND group. Apomorphine-induced rotation tests revealed no rotational bias in the SND group, which persisted for 2 months, but contralateral rotations in the PD group. MicroPET scans revealed glucose hypometabolism and dopamine transporter impairment on the lesioned striatum in the SND group. Tyrosine hydroxylase immunostaining in the SND group revealed that 74.7% of nigral cells on the lesioned side were lost after lesion surgery. These results suggest that the proposed simultaneous double toxin-double lesion method successfully created a rat model of SND that had behavioral outcomes, multitracer microPET evaluation, and histological aspects consistent with SND pathology. This model will be useful for future study of SND.
AuthorsHyung Ho Yoon, Yong Hwan Kim, Eun Sil Shin, Sang Ryong Jeon
JournalJournal of Korean medical science (J Korean Med Sci) Vol. 29 Issue 11 Pg. 1555-61 (Nov 2014) ISSN: 1598-6357 [Electronic] Korea (South)
PMID25408589 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Dopamine Plasma Membrane Transport Proteins
  • Levodopa
  • Oxidopamine
  • Quinolinic Acid
  • Glucose
  • Apomorphine
Topics
  • Animals
  • Apomorphine (pharmacology)
  • Behavior, Animal (drug effects)
  • Corpus Striatum (drug effects, pathology)
  • Disease Models, Animal
  • Dopamine Plasma Membrane Transport Proteins (metabolism)
  • Glucose (metabolism)
  • Injections, Intraperitoneal
  • Levodopa (pharmacology)
  • Male
  • Medial Forebrain Bundle (drug effects, pathology)
  • Oxidopamine (toxicity)
  • Parkinson Disease (metabolism, pathology)
  • Positron-Emission Tomography
  • Quinolinic Acid (toxicity)
  • Rats
  • Rats, Wistar
  • Striatonigral Degeneration (chemically induced, metabolism, pathology)
  • Touch (drug effects)

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