Cyclosporine-A increases locomotor activity in rats with 6-hydroxydopamine-induced hemiparkinsonism: relevance to neural transplantation.
BACKGROUND
The immunosuppressant cyclosporine-A (CsA) is the primary drug for neural transplantation in Parkinson's disease. However, little is known of its direct effects on movement disorders. Our previous observation of increased locomotor activity in normal rats injected with CsA prompted us to investigate further the effects of CsA on hemiparkinsonian rats.


METHODS
We examined the effects of CsA with 6-hydroxydopamine-induced hemiparkinsonism. The animals were randomly assigned to either intraperitoneal injections of CsA (15 mg/kg) or olive oil (the vehicle used for CsA) for 32 days. All animals were tested using the elevated body swing test, and the spontaneous and the amphetamine-induced rotational tests prior to and following the 32-day drug regimen.


RESULTS
As revealed by the elevated body swing test, CsA-treated rats had significantly higher mean percent contralateral (to the lesion) swings compared to their pretreatment level (p < 0.01) or to vehicle-treated rats at posttreatment (p < 0.005). In the spontaneous rotational test, CsA-treated rats displayed ipsilateral (to the lesion) rotations which were significantly higher than their pretreatment rotational behavior (p < 0.005) or the posttreatment rotational behavior of olive oil-treated rats (p < 0.0001). Similarly, CsA-treated rats displayed significantly more amphetamine-induced ipsilateral rotations compared to their or the olive oil-treated rats pretreatment level (p < 0.05).


CONCLUSIONS
Our present observations extend our previous findings on motor alterations produced by CsA on normal rats to hemiparkinsonian rats. These results taken together would suggest that CsA may interact with the locomotor effects observed following neural transplantation with adjunctive CsA immunosuppression.
Borlongan
C V
CV
Departments of Surgery, University of South Florida, College of Medicine, Tampa, USA.
Freeman
T B
TB
Hauser
R A
RA
Cahill
D W
DW
Sanberg
P R
PR
D000818:Animals; D001921:Brain / Q000601:surgery*; D016572:Cyclosporine / Q000494:pharmacology*; D003913:Dextroamphetamine / Q000378:metabolism; D018491:Dopamine Agonists / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008124:Locomotion / Q000187:drug effects*; D008297:Male; D016627:Oxidopamine / Q000009:adverse effects*; D010300:Parkinson Disease / Q000209:etiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016378:Tissue Transplantation
D018491:Dopamine Agonists; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D016627:Oxidopamine; D003913:Dextroamphetamine