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

The detrimental effect of levodopa on behavioral efficacy of fetal dopamine neuron grafts in rats... 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 This suggests that grafted neurons can recover functionally after levodopa treatment is withdrawn, which may be of significance in clinical transplantation trials. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Brain Research Elsevier

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

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Publisher
Elsevier
Copyright
Copyright © 1995 Elsevier Science B.V. All rights reserved
ISSN
0006-8993
D.O.I.
10.1016/0006-8993(95)00149-K
Publisher site
See Article on Publisher Site

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.

Journal

Brain ResearchElsevier

Published: Apr 10, 1995

References

  • Motor function, graft survival and gliosis in rats with 6-OHDA lesions and foetal ventral mesencephalic grafts chronically treated with l -dopa and carbidopa
    Blunt, S.B.; Jenner, P.; Marsden, C.D.
  • Neurotoxicity of levodopa on catecholamine-rich neurons
    Mena, M.A.; Pardo, B.; Casarejos, M.J.; Fahn, S.; de Yebenes, J.G.
  • Chronic levodopa impairs the recovery of dopamine agonist-induced rotational behavior following neural grafting
    Yurek, D.; Steece-Collier, K.; Collier, T.J.; Sladek, J.R.

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