Article date: 1992/2/1
PubMed ID: 1531196
Journal name: Experimental neurology (ISSN: 0014-4886)
The functional status of the dopaminergic system following striatal excitotoxic lesions was studied in living baboons by positron emission tomography (PET) using 6-[18F]fluoro-L-dopa as specific tracer for the presynaptic dopaminergic terminals and [76Br]bromolisuride as selective dopamine D2-receptor marker. The glutamate receptor agonist ibotenic acid (IA) was injected into the right caudate-putamen of six baboons to induce a neuropathological and behavioral model of Huntington's disease (HD). In vivo PET studies performed 3 to 6 months after the IA injections showed that subtotal excitotoxic lesions of the CP were accompanied by changes in the kinetic of [76Br]bromolisuride binding indicating a dose-dependent reduction in binding sites in the lesioned striatum of all IA-injected animals. In the most severely lesioned animals, there was also a decrease in the uptake of the nigrostriatal dopaminergic marker. The loss of D2-receptors and decrease in striatal dopamine uptake are consistent with clinical and postmortem findings in HD. In addition, the decrease in 6-[18F]fluoro-L-dopa uptake confirms previous studies performed in a rat model of HD suggesting a continuous decline of nigral dopamine cell function following destruction of their intrinsic striatal target neurons. The results of our experience to date in PET studies of 6-[18F]fluoro-L-dopa and [76Br]bromolisuride binding in IA-lesioned primates indicate that PET can identify effects of cell loss on markers of pre- and postsynaptic function in the striatum of living subjects.
Author List: Hantraye P, Loc'H C, Maziere B, Khalili-Varasteh M, Crouzel C, Fournier D, Yorke J C, Stulzaft O, Riche D, Isacson O
Publication Types: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.
Substances mentioned in the article: Bromine Radioisotopes; Fluorine Radioisotopes; Receptors, Dopamine; Receptors, Dopamine D2; Ibotenic Acid; 5-fluorodopa; Dihydroxyphenylalanine; Lisuride; bromerguride;
Mesh terms: Animals; Biological Transport; Bromine Radioisotopes; Caudate Nucleus/diagnostic imaging; Dihydroxyphenylalanine/analogs & derivatives; Fluorine Radioisotopes; Ibotenic Acid/toxicity; Kinetics; Lisuride/analogs & derivatives; Papio; Putamen/diagnostic imaging; Receptors, Dopamine/drug effects; Receptors, Dopamine D2; Tomography, Emission-Computed;