Chronic treatment of aged mice with L-deprenyl produces marked striatal MAO-B inhibition but no beneficial effects on survival, motor performance, or nigral lipofuscin accumulation.
Male C57BL/6J mice were provided I-deprenyl (at 0, 0.5 mg/kg or 1.0 mg/kg per day) in their drinking water beginning at 18 months of age. A battery of motor tests, including open-field, tightrope, rotorod, inclined screen, runwheel, and rotodrum tests, was administered before treatment and then 6 months later at 24 months of age. A subsample of mice was retested again at 27 months of age. An untreated group of 9-month-old mice served as young controls. Deprenyl treatment reduced striatal MAO-B activity by up to 60% after 6 months on treatment but had no significant effects on striatal catecholamine levels. No significant effects of deprenyl treatment were observed on body weight, fluid intake, or survival of the mice. Chronic deprenyl treatment also did not affect motor performance in any test, except rotodrum performance at 27 months of age, which was significantly better in the 1.0 mg/kg group treated group compared to controls. No age or deprenyl effects were observed with respect to cell counts in the substantia nigra. However, nigral cells containing lipofuscin increased with age, but this neurohistochemical parameter was also unaffected by deprenyl treatment.
Ingram
D K
DK
Molecular Physiology and Genetics Section, Nathan W. Shock Laboratories, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224.
Wiener
H L
HL
Chachich
M E
ME
Long
J M
JM
Hengemihle
J
J
Gupta
M
M
D000375:Aging / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002395:Catecholamines / Q000378:metabolism; D003216:Conditioning, Operant / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects / Q000201:enzymology*; D004298:Dopamine / Q000378:metabolism; D004326:Drinking / Q000187:drug effects; D008062:Lipofuscin / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D004856:Postural Balance / Q000187:drug effects; D011597:Psychomotor Performance / Q000187:drug effects*; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism; D012642:Selegiline / Q000494:pharmacology*; D013378:Substantia Nigra / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*
D002395:Catecholamines; D008062:Lipofuscin; D008996:Monoamine Oxidase Inhibitors; D011954:Receptors, Dopamine; D012642:Selegiline; D008995:Monoamine Oxidase; D004298:Dopamine