Volume transmission of dopamine over large distances may contribute to recovery from experimental parkinsonism.
Administration of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to cats results in a parkinsonian syndrome that spontaneously recovers by 6 weeks after induction. Striatal dopamine depletions in these animals are heterogenous with more extensive damage dorsolaterally than ventromedially. Measures of extracellular dopamine levels by in vivo microdialysis showed that dopamine released from a relatively preserved ventral striatal innervation can diffuse over a distance of 5.5 mm to 7.0 mm to the more extensively denervated dorsolateral striatum, where it may influence sensorimotor activities and contribute to functional recovery. Diffusion of dopamine through a large volume of striatal tissue was observed in cats 6 weeks after an MPTP-induced lesion and in normal cats with pharmacologically induced dopamine reuptake inhibition, but not in normal animals without reuptake inhibition. In cats recovered from MPTP-induced parkinsonism, a greater amount of dopamine was recovered from the extracellular fluid in the dorsolateral caudate following stimulated release of dopamine from the ventromedial striatum than after stimulated release locally in the dorsolateral caudate. These results suggest volume transmission of dopamine over large distances is possible and perhaps an important contributor to functional recovery from a large dopamine-depleting lesion. These results may also form the basis for understanding how limited reinnervation of the striatum by grafts or trophic factor therapies may lead to significant functional improvement.
Schneider
J S
JS
Department of Neurology, Hahnemann University School of Medicine, Philadelphia, PA 19102.
Rothblat
D S
DS
DiStefano
L
L
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D002415:Cats; D002421:Caudate Nucleus / Q000378:metabolism*; D003342:Corpus Striatum / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D005110:Extracellular Space / Q000378:metabolism; D017551:Microdialysis; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000503:physiopathology*; D013997:Time Factors
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine