Inhibition of monoamine oxidase-B by (-)-deprenyl potentiates neuronal responses to dopamine agonists but does not inhibit dopamine catabolism in the rat striatum.
This report describes experiments designed to determine whether (-)-deprenyl potentiates dopaminergic transmission and whether its mechanism involves the inhibition of dopamine catabolism. Intraperitoneal administration of (-)-deprenyl (0.5-8 mg kg-1) produced a dose-dependent inhibition of striatal monoamine oxidase type B activity whereas monamine oxidase type A activity in the striatum was inhibited only by 8 mg kg-1 of (-)-deprenyl. Intraperitoneal administration of (-)-deprenyl (0.5-4 mg kg-1) did not alter the striatal concentrations of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) or homovanillic acid. DOPAC concentrations were decreased by 8 mg kg-1 of (-)-deprenyl. In contrast, administration of clorgyline (2 mg kg-1), a monoamine oxidase type A inhibitor, increased the striatal concentrations of DA and decreased the striatal concentrations of DOPAC and homovanillic acid. The striatal concentrations of 2-phenylethylamine (PE), a putative modulator of striatal DA transmission, were increased by (-)-deprenyl (1-8 mg kg-1) but were unaffected by clorgyline (2 mg kg-1). In electrophysiological studies, single caudate neuron responses to iontophoretically applied (-)-apomorphine and (+/-)-2-(N-phenethyl-N-propyl) amino-5-hydroxytetralin were potentiated by intracarotid injections of PE (30 micrograms kg-1) and i.p. injections of (-)-deprenyl (2 mg kg-1). Both PE and (-)-deprenyl reduced the IT50 of responses to apomorphine and (+/-)-2-(N-phenethyl-N-propyl)amino-5-hydroxytetralin.(ABSTRACT TRUNCATED AT 250 WORDS)
Neuropsychiatric Research Unit, University of Saskatchewan, Saskatoon, Canada.
I A
IA
Paterson
A V
AV
Juorio
M D
MD
Berry
M Y
MY
Zhu
D000818:Animals; D001679:Biogenic Amines / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism* / Q000502:physiology; D015259:Dopamine Agents / Q000494:pharmacology; D004357:Drug Synergism; D008297:Male; D008995:Monoamine Oxidase / Q000187:drug effects / Q000378:metabolism; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D010627:Phenethylamines / Q000494:pharmacology; D011619:Psychotropic Drugs / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects / Q000502:physiology; D012642:Selegiline / Q000494:pharmacology*; D009435:Synaptic Transmission / Q000187:drug effects
D001679:Biogenic Amines; D015259:Dopamine Agents; D008996:Monoamine Oxidase Inhibitors; D010627:Phenethylamines; D011619:Psychotropic Drugs; D011954:Receptors, Dopamine; D012642:Selegiline; C029261:phenethylamine; D008995:Monoamine Oxidase; D004298:Dopamine