Dopamine fiber growth induction by implantation of synthetic dopamine-containing microspheres in rats with experimental hemi-parkinsonism.
Injectable local drug delivery formulations-so-called microspheres have recently been developed, in which drugs are microencapsulated within biocompatible and biodegradable copolymer excipients like poly[DL-lactide-co-glycolide]. In view of its potential therapeutical usefulness, we have studied the microsphere methodology as a means to substitute for experimentally induced subnormal levels of endogenous dopamine (DA). Administration of 6-hydroxydopamine (6-OH-DA) unilaterally in the medial forebrain bundle of rats results in an up-regulation of postsynaptic receptors in the denervated striatum, functionally manifested as contralateral rotational behavior after apomorphine. DA microspheres were implanted in the denervated striatum. The majority of the rats displayed an attenuation of the contralateral rotational behavior induced by apomorphine up to 8 wk postimplantation. Immunocytochemical observations unexpectedly demonstrated growth of DA and tyrosine hydroxylase immunoreactive fibers in the denervated striatum. Interestingly, there was an apparent correlation between functional recovery and the degree of growth of DA fibers. The present results suggest that implantation of DA microspheres may promote DA fiber growth and extended recovery of surviving DA neurons, and, therefore, could be of therapeutic usefulness in Parkinson's disease.
McRae
A
A
Department of Histology, University of Göteborg, Sweden.
Hjorth
S
S
Dahlström
A
A
Dillon
L
L
Mason
D
D
Tice
T
T
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000473:pathology*; D004298:Dopamine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D004339:Drug Compounding; D004343:Drug Implants; D008297:Male; D009416:Nerve Regeneration / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000032:analysis; D016627:Oxidopamine / Q000633:toxicity; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D011954:Receptors, Dopamine / Q000096:biosynthesis; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis; D015854:Up-Regulation / Q000187:drug effects
D004343:Drug Implants; D009419:Nerve Tissue Proteins; D011954:Receptors, Dopamine; D016627:Oxidopamine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine