Selective inhibition of MAO-B through chronic low-dose (R)-deprenyl treatment in C57BL/6 mice has no effect on basal neostriatal dopamine levels.
C. Thiffault, L. Lamarre-Théroux, R. Quirion, and J. Poirier (1997, Mol. Brain Res. 44: 238-244) recently reported that chronic treatment of young (12 week old) C57BL/6 mice with (R)-deprenyl, a mechanism-based inactivator of monoamine oxidase B (MAO-B), leads to a more than fourfold increase in neostriatal dopamine levels. Such an effect could complicate the interpretation of results obtained from mechanistic studies designed to evaluate the putative neuroprotective effects of (R)-deprenyl in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned mice. In contrast to the results of Thiffault et al., we have found that neostriatal dopamine levels in mature (32 week old) C57BL/6 mice were unaltered by chronic (R)-deprenyl treatment even though brain monoamine oxidase B activity was reduced by more than 80%. Neostriatal dopamine levels also were unaltered in both young and mature mice when the (R)-deprenyl treatment period was doubled compared to that reported by Thiffault et al. Consequently, studies on the putative neuroprotective properties of (R)-deprenyl in MPTP-lesioned mice are unlikely to be complicated by the possibility that inhibition of MAO-B alone will lead to an increase in neostriatal dopamine levels.
Steyn
S J
SJ
Harvey W. Peters Center, Virginia Tech, Blacksburg, Virginia 24061-0212, USA.
Castagnoli
K
K
Steyn
S
S
Castagnoli
N
N
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000293:injuries / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008995:Monoamine Oxidase / Q000187:drug effects*; D008996:Monoamine Oxidase Inhibitors / Q000008:administration & dosage*; D018696:Neuroprotective Agents / Q000008:administration & dosage; D020734:Parkinsonian Disorders; D012642:Selegiline / Q000008:administration & dosage*
D015259:Dopamine Agents; D008996:Monoamine Oxidase Inhibitors; D018696:Neuroprotective Agents; D012642:Selegiline; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D008995:Monoamine Oxidase; D004298:Dopamine