The detrimental effect of levodopa on behavioral efficacy of fetal dopamine neuron grafts in rats is reversible following prolonged withdrawal of chronic dosing.
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 This suggests that grafted neurons can recover functionally after levodopa treatment is withdrawn, which may be of significance in clinical transplantation trials.
Steece-Collier
K
K
Department of Neurology, University of Rochester School of Medicine, NY 14642, USA.
Yurek
D M
DM
Collier
T J
TJ
Junn
F S
FS
Sladek
J R
JR
D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D004334:Drug Administration Schedule; D016332:Fetal Tissue Transplantation; D007980:Levodopa / Q000009:adverse effects*; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects* / Q000637:transplantation; D051381:Rats; D011916:Rats, Inbred F344; D012399:Rotation; D013375:Substance Withdrawal Syndrome; D013997:Time Factors
D007980:Levodopa; D004298:Dopamine