Selective Inhibition of MAO-B through Chronic Low-Dose (R)-Deprenyl Treatment in C57BL/6 Mice Has No Effect on Basal Neostriatal Dopamine Levels

• Published in: Experimental neurology 2001-04, Vol.168 (2), p.434-436
• Main Authors: Steyn, Stefanus J., Castagnoli, Kay, Steyn, Salome, Castagnoli, Neal
• Format: Article
• Language: English
• Subjects: (R)-deprenyl; 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Animals; Biological and medical sciences; C57BL/6 mouse; Corpus Striatum - drug effects; Corpus Striatum - injuries; Corpus Striatum - metabolism; dopamine; Dopamine - metabolism; Dopamine Agents; Male; Medical sciences; Mice; Mice, Inbred C57BL; monoamine oxidase; Monoamine Oxidase - drug effects; Monoamine Oxidase Inhibitors - administration & dosage; neuronal degeneration; Neuropharmacology; Neuroprotective agent; Neuroprotective Agents - administration & dosage; Parkinsonian Disorders; Pharmacology. Drug treatments; Selegiline - administration & dosage
• ISSN: 0014-4886; 1090-2430
• DOI: 10.1006/exnr.2000.7610

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.