Experimental hemiparkinsonism in the rat following chronic unilateral infusion of MPP+ into the nigrostriatal dopamine pathway--II. Differential localization of dopamine and cholecystokinin receptors.
The autoradiographical localization of dopamine D1, D2 and cholecystokinin receptors has been investigated in rat brain 6 months following unilateral infusion of 1-methyl-4-phenyl pyridinium ion (MPP+) (10 micrograms/day for 7 days) into the nigrostriatal dopamine pathway. Treatment with 1-methyl-4-phenyl pyridinium ion produced a marked depletion of dopamine cell bodies in the substantia nigra together with greater than 95% loss of tyrosine hydroxylase immunoreactivity in the striatum. Measurement of specific [3H]spiperone binding to D2 receptors indicated a 38% increase (P less than 0.01) in the maximal binding capacity of [3H]spiperone to striatal membrane homogenates and a 13% increase (P less than 0.05) in specific [3H]spiperone binding to striatal tissue sections, verifying striatal D2 receptor denervation supersensitivity. In contrast, MPP+ lesion of the nigrostriatal tract had no effect on the autoradiographical localization of striatal D1 or cholecystokinin receptors. In addition, there was a 38% loss (P less than 0.05) of D2 receptor binding sites in the substantia nigra pars compacta, whilst D1 receptors remained unchanged. Similar changes in dopamine and cholecystokinin receptor number were found following 6-hydroxydopamine lesion of the nigrostriatal dopamine pathway. These results provide further evidence that 1-methyl-4-phenyl pyridinium ion treatment in rats produces extensive destruction of the dopaminergic nigrostriatal tract and supports the differential anatomical localization of striatal and nigral D1, D2 and cholecystokinin receptors.
Beresford
I J
IJ
Parke-Davis Research Unit, Addenbrookes Hospital Site, Cambridge, U.K.
Davenport
A P
AP
Sirinathsinghji
D J
DJ
Hall
M D
MD
Hill
R G
RG
Hughes
J
J
D015655:1-Methyl-4-phenylpyridinium; D000818:Animals; D001345:Autoradiography; D001552:Benzazepines / Q000031:analogs & derivatives* / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D007839:Functional Laterality; D007091:Image Processing, Computer-Assisted; D008297:Male; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D011726:Pyridinium Compounds / Q000633:toxicity*; D051381:Rats; D011919:Rats, Inbred Strains; D011949:Receptors, Cholecystokinin / Q000378:metabolism*; D011954:Receptors, Dopamine / Q000378:metabolism*; D012844:Sincalide / Q000378:metabolism; D013134:Spiperone / Q000378:metabolism; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology
C049558:8-iodo-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepine-7-ol; D001552:Benzazepines; D011726:Pyridinium Compounds; D011949:Receptors, Cholecystokinin; D011954:Receptors, Dopamine; D013134:Spiperone; D012844:Sincalide; D015655:1-Methyl-4-phenylpyridinium