ALTERATIONS IN DOPAMINE UPTAKE SITES AND D1 AND D2 RECEPTORS IN CATS SYMPTOMATIC FOR AND RECOVERED FROM EXPERIMENTAL PARKINSONISM

The administration of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahy dropyridine (MPTP) to adult cats severely disrupts the dopaminergic in nervation of the striatum. Animals display a parkinson-like syndrome, consisting of akinesia, bradykinesia, postural instability, and rigidi ty, which spontaneously recovers by 4-6 weeks after the last administr ation of MPTP. In this study we used quantitative receptor autoradiogr aphy to examine changes in DA uptake sites and DA receptors in the bas al ganglia of normal, and symptomatic and recovered MPTP-treated cats. Consistent with the destruction of the nigrostriatal DA pathway, ther e was a severe loss of DA uptake sites, labeled with [H-3]-mazindol, i n the caudate nucleus (64-82%), nucleus accumbens (44%), putamen (63%) , and substantia nigra pars compacta (SNc, 53%) of symptomatic cats. F ollowing behavioral recovery, there were no significant changes in DA uptake site density. Significant increases of [H-3]-SCH 23390 binding to D1 DA receptors were observed in the dorsal caudate (> 24%; P < 0.0 5) of symptomatic cats and in all regions of the caudate-putamen (> 30 %; P < 0.05) of recovered animals. [H-3]-SCH 23390 binding in the subs tantia nigra pars reticulata was half of that in the striatum and show ed no changes in symptomatic or recovered animals. No alterations in t he binding of [I-125]-epidepride to D2 receptors was observed in any r egion of the striatum in either symptomatic or recovered animals. [I-1 25]-Epidepride binding in the SNc was decreased by > 36% (P < 0.05) fo llowing MPTP treatment. These data show that cats made parkinsonian by MPTP exposure have a significant decrease in the number of DA reuptak e sites throughout the striatum and that recovery of sensorimotor func tion in these animals is not correlated with an increase in the number of striatal reuptake sites. Behavioral recovery, however, does seem t o be correlated with a general elevation of D1 receptors throughout th e striatal complex. The present data also show that direct correlation s between changes in DA receptor regulation after a large DA depleting lesion and behavioral deficits or recovery from those deficits are di fficult and that the relationships between DA receptors/transporters a nd behavior require further study. (C) 1995 Wiley-Liss, Inc.