An encapsulated dopamine-releasing polymer alleviates experimental parkinsonism in rats.
The effect of sustained intrastriatal release of dopamine (DA) from polymer matrices on apomorphine-induced turning behavior in a 6-hydroxydopamine (6-OHDA) unilaterally lesioned rat model was analyzed. A biocompatible semipermeable tube was placed in a denervated striatum as a receptacle for DA-releasing polymer rods. In vitro kinetics showed sustained release of DA from a polymeric rod for 15 days. Implantation of a DA-releasing rod within the striatal receptacle significantly decreased apomorphine-induced rotational behaviour in lesioned animals. Upon removal of the DA-releasing system from the receptacle, rotational behaviour increased within 2 weeks and approached preimplant control values 4 weeks later. Acute microdialysis revealed that DA appeared in the extracellular space within 20 min after the implantation of a DA-releasing rod into a denervated striatum. Significant DA amounts were still measurable 7 days postimplantation, indicating sustained DA release from the polymer rod. Dopamine released from a polymer matrix through a semipermeable receptacle alleviates experimental parkinsonism in rats, suggesting that controlled intrastriatal release of DA from a polymer matrix may provide an alternative method for the treatment of Parkinson's disease.
Winn
S R
SR
Artificial Organ Laboratory, Brown University, Providence, Rhode Island 02912.
Wahlberg
L
L
Tresco
P A
PA
Aebischer
P
P
D000180:Acrylic Resins; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001921:Brain / Q000473:pathology; D003342:Corpus Striatum / Q000187:drug effects; D004195:Disease Models, Animal; D004298:Dopamine / Q000008:administration & dosage* / Q000627:therapeutic use; D004343:Drug Implants; D006892:Hydroxydopamines; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D016627:Oxidopamine; D010300:Parkinson Disease / Q000473:pathology; D010302:Parkinson Disease, Secondary / Q000188:drug therapy*; D011145:Polyvinyls; D051381:Rats; D011919:Rats, Inbred Strains
D000180:Acrylic Resins; D004343:Drug Implants; D006892:Hydroxydopamines; D011145:Polyvinyls; D016627:Oxidopamine; D001058:Apomorphine; D004298:Dopamine