TY - JOUR
T1 - Pharmacological effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on striatal dopamine receptor system
AU - Lau, Yuen Sum
AU - Fung, Yiu K.
N1 - Funding Information:
This research was supported in part by a BRS grant from NIH to Creighton University and by a Grant R03 MH38159-01 from the National Institute of Mental Health. The technical support from Mr. C. Runice is gratefully acknowledged. We thank Drs. Thomas E. Donnelly, Jr. and John A. Wilson for their advice during the preparation of this manuscript, Ms. C. Forward for typing the manuscript.
PY - 1986/3/26
Y1 - 1986/3/26
N2 - In mice, chronic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) produces an increase in the maximum number of [3H]spiperone binding sites in the striatum. The sensitivity of striatal protein phosphorylation to calcium plus calmodulin is also potentiated in MPTP-treated mice. These observations are associated with an enhancement of apomorphine-induced climbing behavior in the drug-treated animals. The results of this study suggest that in an animal model for Parkinson's disease, MPTP interrupts the dopamine (DA) transmission by chemically denervating the nigrostriatal neurons and through a compensatory mechanism, it increases the number of DA receptors as well as the sensitivity of protein phosphorylation to calcium plus calmodulin in mouse striatum. The latter two events may contribute to the development of DA receptor supersensitivity.
AB - In mice, chronic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) produces an increase in the maximum number of [3H]spiperone binding sites in the striatum. The sensitivity of striatal protein phosphorylation to calcium plus calmodulin is also potentiated in MPTP-treated mice. These observations are associated with an enhancement of apomorphine-induced climbing behavior in the drug-treated animals. The results of this study suggest that in an animal model for Parkinson's disease, MPTP interrupts the dopamine (DA) transmission by chemically denervating the nigrostriatal neurons and through a compensatory mechanism, it increases the number of DA receptors as well as the sensitivity of protein phosphorylation to calcium plus calmodulin in mouse striatum. The latter two events may contribute to the development of DA receptor supersensitivity.
KW - 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)
KW - [H]spiperone binding site
KW - apomorphine-stimulated-climbing behavior
KW - calmodulin-dependent phosphorylation
KW - dopamine receptor supersensitivity
KW - striatum
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U2 - 10.1016/0006-8993(86)90541-X
DO - 10.1016/0006-8993(86)90541-X
M3 - Article
C2 - 3486026
AN - SCOPUS:0022549418
VL - 369
SP - 311
EP - 315
JO - Brain Research
JF - Brain Research
SN - 0006-8993
IS - 1-2
ER -