The vesamicol receptor ligand (+)-meta-[125I]iodobenzyltrozamicol [(+)-[125I]-MIBT] reveals blunting of the striatal cholinergic response to dopamine D2 receptor blockade in the 6-hydroxydopamine (6-OHDA)-lesioned rat: possible implications for Parkinson's disease.
Previous studies of radiolabelled vesamicol receptor (VR) ligands suggest that the latter may be used, in conjunction with dopamine D2 antagonists, to measure changes in striatal cholinergic function in vivo. In the present study, the radiolabelled VR ligand (+)-meta-[125I]iodobenzyltrozamicol {(+)-[125I]MIBT} was used to assess striatal cholinergic function in the unilateral 6-hydroxydopamine (6-OHDA)-treated rat. In control animals, the levels of this radiotracer monitored at 3 hr post injection displayed bilateral symmetry in the striatum, cerebral cortex and cerebellum. However, in animals pretreated with the dopamine antagonist spiperone (2 mg/kg ip), the radiotracer concentration in the striatal hemisphere ipsilateral to 6-OHDA lesion increased by 23% (p = 0.068) while the concentration in the contralateral striatum was elevated by 87% (p < 0.0001). Since the nigrostriatal dopaminergic system modulates striatal cholinergic function, and dopamine D2 receptor blockade is known to result in increased striatal cholinergic function, the refractoriness of striatal cholinergic neurons following the loss of nigrostriatal dopaminergic innervation confirms the existence of a dopaminergic-cholinergic imbalance in Parkinson's disease. Therefore the combination of a D2 antagonist and radiolabelled VR ligand may provide a potentially useful method for assessing the effects of dopamine depletion in Parkinson's disease.
Efange
S M
SM
Department of Radiology, University of Minnesota, Minneapolis 55455, USA.
Langason
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RB
Khare
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Low
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WC
D000818:Animals; D001927:Brain Diseases / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D002799:Cholinergic Fibers / Q000187:drug effects / Q000502:physiology*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D004195:Disease Models, Animal; D018492:Dopamine Antagonists / Q000494:pharmacology*; D065127:Dopamine D2 Receptor Antagonists; D007457:Iodine Radioisotopes; D007462:Iodobenzenes / Q000378:metabolism* / Q000493:pharmacokinetics; D008024:Ligands; D008297:Male; D016627:Oxidopamine / Q000633:toxicity; D010300:Parkinson Disease / Q000378:metabolism / Q000503:physiopathology*; D010880:Piperidines / Q000378:metabolism* / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D011950:Receptors, Cholinergic / Q000378:metabolism*; D013134:Spiperone / Q000494:pharmacology*
D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D007457:Iodine Radioisotopes; D007462:Iodobenzenes; D008024:Ligands; D010880:Piperidines; D011950:Receptors, Cholinergic; C083232:vesamicol receptor; C081671:(3-iodobenzyl)trozamicol; D013134:Spiperone; D016627:Oxidopamine