Effects of D1 and D2 agonists on spontaneous motor activity in MPTP treated mice.
Two experiment were performed to study the effect of combining bromocriptine with SKF 38393 (SKF), or vice/versa, upon parameters of spontaneous motor activity in MPTP treated and saline (control) treated mice. Treatment with MPTP (2 x 40 mg/kg, subcutaneously) induced a hypoactive condition compared with saline treated mice. Bromocriptine (10 mg/kg, subcutaneously), administered to MPTP mice 2 hr, but not 1 or 4 hr, after SKF (6 mg/kg, subcutaneously) caused a marked increase in locomotion and rearing behaviour. The administration of bromocriptine (10 mg/kg, subcutaneously) 4 hr before SKF (6 mg/kg, subcutaneously) elevated all three parameters of spontaneous activity in the MPTP treated mice, independent of the injection of SKF. Bromocriptine injection 1 or 2 hr before SKF decreased locomotion in both MPTP and control mice. Neurochemical analysis confirmed the dopamine depletion in the MPTP treated mice. These results are discussed in terms of the reliability of the MPTP model of parkinsonism in mice and the dopamine D1/D2 receptor hypersensitivity following denervation with the neurotoxin.
Department of Toxicology, Uppsala University, Sweden.
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Fredriksson
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Plaznik
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Sundström
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Archer
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology*; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects; D001971:Bromocriptine / Q000494:pharmacology*; D004338:Drug Combinations; D008124:Locomotion / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects*; D017447:Receptors, Dopamine D1 / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000378:metabolism
D004338:Drug Combinations; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D001971:Bromocriptine; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine