Biochemical and behavioral recovery in a rodent model of Parkinson's disease following stereotactic implantation of dopamine-containing liposomes.
We have developed and characterized dopamine-containing liposomes which exhibited in vitro sustained release of dopamine for over 40 days. These liposomes were stereotactically implanted into the partially denervated corpus striatum of rats subjected to unilateral lesions of the substantia nigra. In vivo release of dopamine into striatal extracellular fluid was monitored by microdialysis and behavior was assessed by quantifying apomorphine-induced asymmetric rotation. Extracellular dopamine levels in the partially denervated striatum of the dopamine liposome-treated rats were greater than the levels in the lesioned rats which received control liposomes and these levels remained elevated for 25 days. In parallel, those rats which received dopamine liposomes exhibited partial behavioral recovery, with attenuation of asymmetric rotation following systemic apomorphine administration. These results suggest that dopamine-containing liposomes can partially ameliorate the deficits associated with a rodent model of Parkinson's disease, and demonstrate the potential of this technology as a method for the controlled delivery of therapeutic agents into discrete areas of the brain.
During
M J
MJ
Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06510.
Freese
A
A
Deutch
A Y
AY
Kibat
P G
PG
Sabel
B A
BA
Langer
R
R
Roth
R H
RH
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D003342:Corpus Striatum / Q000378:metabolism; D003692:Delayed-Action Preparations; D004298:Dopamine / Q000008:administration & dosage* / Q000378:metabolism / Q000627:therapeutic use; D004337:Drug Carriers; D006892:Hydroxydopamines / Q000633:toxicity; D008081:Liposomes; D008297:Male; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D051381:Rats; D011919:Rats, Inbred Strains; D013238:Stereotaxic Techniques; D013239:Stereotyped Behavior / Q000187:drug effects*; D013378:Substantia Nigra / Q000187:drug effects / Q000473:pathology
D003692:Delayed-Action Preparations; D004337:Drug Carriers; D006892:Hydroxydopamines; D008081:Liposomes; C027802:5-hydroxydopamine; D001058:Apomorphine; D004298:Dopamine