Effect of MPTP on Dopamine D2 Receptors in the Aging Mouse Striatum
Recently, MPTP (1-methyl, 4-phenyl-1, 2, 3, 6-tetrahydropyridine) present as a contaminant in a synthetic heroin, produced a Parkinson-like disorder following intravenous administration and caused destruction of the nigrostriatal dopamine system in humans (Davis et al. 1979; Langston et al. 1983; Langston and Ballard, 1985). Studies in non-human primates and mice revealed similar degenerative effects of MPTP in the nigrostriatal system (Burns et al. 1983, Heikkila et al. 84, Gupta et al. 1984). Furthermore, it has been shown that aged mice are much more sensitive to MPTP treatment than their younger counterparts treated in a similar manner (Gupta et al. 1986). Degeneration of the dopaminergic nigrostriatal neurons in Parkinson’s disease has been shown to increase the number of dopamine D2 receptors in the striatum (Bokobza et al. 1984; Seeman, 1980). An increase in D2 receptor density in the medial caudate/putamen has also been reported following dopamine denervation with MPTP treatment in monkeys (Joyce et al. 1986). Sershen et al. (1986) reported that MPTP administration in the young adult mice did not alter 3H-spiperone binding in the mouse striatum despite causing a 63% reduction in 3H-dopamine uptake while Pertouka et al. (1988) reported an increase in 3H-spiperone binding 2 days following MPTP treatment. Since our previous studies have shown that aged mice are more sensitive to MPTP treatment, the present study was undertaken to investigate if dopamine D2 receptors are altered in aged mice treated with MPTP. Furthermore, our previous studies have shown the presence of high and low agonist affinity states of D2 receptors; thus, changes in these high and low sites were also investigated in the striatum of aged control and MPTP treated mice.
KeywordsAged Mouse Guanine Nucleotide MPTP Treatment Mouse Striatum MPTP Administration
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