Deprenyl alters behavior and caudate dopamine through an amphetamine-like action.
In vivo microdialysis was used to concurrently measure the behavioral and caudate dopamine (DA) responses to the alleged irreversible type B monoamine oxidase inhibitor deprenyl. The effects were contrasted to those of the type A monoamine oxidase inhibitor, clorgyline. Consistent with its effects as an irreversible monoamine oxidase inhibitor, clorgyline produced an increase in DA concentration that remained elevated for at least 6 h. In contrast, the deprenyl-induced elevation in DA concentration occurred more rapidly, achieved a higher peak response, and then returned to baseline within 2 h following drug administration. The two drugs also produced distinctive changes in DA metabolite levels. Whereas the pattern of clorgyline-induced effects were consistent with irreversible monoamine oxidase inhibition, deprenyl produced an amphetamine-like response profile. Further, deprenyl but not clorgyline significantly increased locomotor activity. These results suggest that deprenyl does not augment caudate DA levels through monoamine oxidase inhibition. Rather, the pattern of its effects on caudate DA dynamics and behavior supports previous evidence that deprenyl produces its effects through its metabolism to amphetamine-like substances.
Okuda
C
C
Department of Psychiatry, University of California, San Diego, La Jolla 92093-0603.
Segal
D S
DS
Kuczenski
R
R
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002421:Caudate Nucleus / Q000187:drug effects / Q000378:metabolism*; D003010:Clorgyline / Q000494:pharmacology; D004298:Dopamine / Q000031:analogs & derivatives / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006719:Homovanillic Acid / Q000378:metabolism; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012642:Selegiline / Q000494:pharmacology*
D015102:3,4-Dihydroxyphenylacetic Acid; D012642:Selegiline; D000661:Amphetamine; C001746:3-methoxytyramine; D003010:Clorgyline; D004298:Dopamine; D006719:Homovanillic Acid