Selegiline long-term effects on brain acetylcholinesterase, (Na+,K+)-ATPase activities, antioxidant status and learning performance of aged rats.
The aim of this study was to investigate the effects of selegiline ((-)deprenyl), an irreversible inhibitor of monoaminoxidase-B (MAO-B): (a) on brain acetylcholinesterase (AChE), (Na(+),K(+))-ATPase and Mg(2+)-ATPase activities; (b) total antioxidant status (TAS); (c) learning performance and to evaluate possible correlation between biochemical and behavioral findings after long-term drug administration in aged male rats. Selegiline (0.25mgkg(-1) rat) was administered once every other day for 50 days. Learning parameters were tested through a two-way active avoidance procedure taking place in an Ugo-Basile automated shuttle box device. Enzyme activities and TAS were evaluated spectrophotometrically in brain homogenates of decapitated animals. TAS was significantly lower in aged compared to adult rats and this was reversed by selegiline administration. The decrease of free radical production by selegiline resulted in the stimulation of AChE and (Na(+),K(+))-ATPase. Mg(2+)-ATPase activity was not affected by the drug. Selegiline seems to improve the avoidance performance as compared to control groups. It is concluded that: (a) MAO-B inhibition and/or free radical protection on tyrosine hydroxylase by the drug may increase brain catecholamine concentrations resulting possibly in (Na(+),K(+))-ATPase stimulation; (b) AChE and (Na(+),K(+))-ATPase activation by the drug could modulate brain cholinergic, catecholaminergic and serotoninergic systems as well as the neural excitability and metabolic energy production; and (c) selegiline seems to improve the learning performance of aged rats.
Carageorgiou
Haris
H
Department of Experimental Pharmacology, Medical School, University of Athens, Athens, Greece.
Zarros
Apostolos
A
Tsakiris
Stylianos
S
D000110:Acetylcholinesterase / Q000378:metabolism*; D000367:Age Factors; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001362:Avoidance Learning / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D017301:Ca(2+) Mg(2+)-ATPase / Q000378:metabolism; D005609:Free Radicals / Q000378:metabolism; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012642:Selegiline / Q000494:pharmacology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D013053:Spectrophotometry
D000975:Antioxidants; D005609:Free Radicals; D008996:Monoamine Oxidase Inhibitors; D012642:Selegiline; D000110:Acetylcholinesterase; D017301:Ca(2+) Mg(2+)-ATPase; D000254:Sodium-Potassium-Exchanging ATPase