THE VESAMICOL RECEPTOR-LIGAND (-META-[I-125]IODOBENZYLTROZAMICOL ((+)-[I-125]-MIBT) REVEALS BLUNTING OF THE STRIATAL CHOLINERGIC RESPONSE TO DOPAMINE D2 RECEPTOR BLOCKADE IN THE 6-HYDROXYDOPAMINE (6-OHDA)-LESIONED RAT - POSSIBLE IMPLICATIONS FOR PARKINSONS-DISEASE())

Previous studies of radiolabelled vesamicol receptor (VR) ligands sugg est that the latter may be used, in conjunction with dopamine D2 antag onists, to measure changes in striatal cholinergic function in vivo. I n the present study, the radiolabelled VR ligand (+)-meta-[I-125]iodob enzyltrozamicol {(+)[I-125]MIBT} was used to assess striatal cholinerg ic function in the unilateral 6-hydroxydopamine (6-OHDA)-treated rat. In control animals, the levels of this radiotracer monitored at 3 hr p ost injection displayed bilateral symmetry in the striatum, cerebral c ortex and cerebellum. However, in animals pretreated with the dopamine antagonist spiperone (2 mg/kg ip), the radiotracer concentration in t he striatal hemisphere ipsilateral to the 6-OHDA lesion increased by 2 3% (p = 0.068) while the concentration in the contralateral striatum w as elevated by 87% (p < 0.0001). Since the nigrostriatal dopaminergic system modulates striatal cholinergic function, and dopamine D2 recept or blockade is known to result in increased striatal cholinergic funct ion, 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. Theref ore, the combination of a D2:antagonist and radiolabelled VR ligand ma y provide a potentially useful method for assessing the effects of dop amine depletion in Parkinson's disease.