The detrimental effect of levodopa on behavioral efficacy of fetal dopamine neuron grafts in rats is reversible following prolonged withdrawal of chronic dosing

Kathy Steece-Collier, David M. Yurek, Timothy J. Collier, Fred S. Junn, John R. Sladek

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

In previous studies, we observed that chronic levodopa treatment resulted in impaired morphology and function of grafted dopamine neurons in rats. To begin to better understand how levodopa treatment might influence dopamine neurons, we examined whether subsequent discontinuation of chronic levodopa treatment might allow for recovery of graft efficacy. Function of embryonic mesencephalic tissue grafts was assessed by monitoring rotational behavior elicited by amphetamine in lesioned, grafted rats initially treated for 6 weeks with levodopa followed by a 6 week drug-free period. As observed previously, control grafted animals, but not levodopa treated animals, showed behavioral improvement. However, following a 6 week withdrawal period, the levodopa animals demonstrated a significant reduction in amphetamine rotations which was reminiscent of control animals. This suggests that grafted neurons can recover functionally after levodopa treatment is withdrawn, which may be of significance in clinical transplantation trials.

Original languageEnglish
Pages (from-to)404-408
Number of pages5
JournalBrain Research
Volume676
Issue number2
DOIs
StatePublished - Apr 10 1995

Bibliographical note

Funding Information:
This research was generously supported by a grant from the United Parkinson Foundation (KS.-C.) and Public Heailth Service Grants AGlOSS to T.J.C. and NS24032 to J.R.S.). The authors would like to acknowledge the excellent technical assistance of Brian Daley and Daniel Jarvis.

Keywords

  • Dopamine neuron
  • Fetal transplant
  • Functional recovery
  • Levodopa
  • Parkinson's disease

ASJC Scopus subject areas

  • General Neuroscience
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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