The effects of administration of monoamine oxidase-B inhibitors on rat striatal neurone responses to dopamine.
1. (-)-Deprenyl has been shown to potentiate rat striatal neurone responses to dopamine agonists at doses not altering dopamine metabolism. Since there are a number of effects of (-)-deprenyl which could result in this phenomenon, we have investigated the effects of MDL 72,145 and Ro 19-6327, whose only common effect with (-)-deprenyl is an inhibition of monoamine oxidase-B (MAO-B), on rat striatal neurone responses to dopamine and on striatal dopamine metabolism. 2. Using in vivo electrophysiology, i.p. injection of either MDL 72,145 or Ro 19-6327 was found to produce a dose-dependent potentiation of striatal neurone responses to dopamine but not gamma-aminobutyric acid. 3. Neurochemical investigations revealed that this occurred at doses (0.25-1 mg kg-1) which, while not affecting levels of dopamine or its metabolites, 3,4-dihydroxyphenylacetic acid or homovanillic acid, did cause a significant, dose-dependent, elevation in striatal levels of the putative neuromodulator, 2-phenylethylamine (PE). 4. Inhibition of PE synthesis by i.p. injection of the aromatic L-amino acid decarboxylase inhibitor, NSD 1015, produced a reversal of the effects of MDL 72,145 and Ro 19-6327. 5. Neurochemical analysis revealed this to occur at a dose of NSD 1015 (10 mg kg-1) selective for reduction of elevated PE levels. 6. These results suggest that PE can act as a neuromodulator of dopaminergic responses and that MAO-B inhibitors may potentiate neuronal responses to dopamine via the indirect mechanism of elevation of PE following MAO-B inhibition.
Berry
M D
MD
Neuropsychiatric Research Unit, University of Saskatchewan, Saskatoon, Canada.
Scarr
E
E
Zhu
M Y
MY
Paterson
I A
IA
Juorio
A V
AV
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000499:Allylamine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D003342:Corpus Striatum / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism* / Q000494:pharmacology; D004594:Electrophysiology; D006719:Homovanillic Acid / Q000378:metabolism; D006834:Hydrazines / Q000494:pharmacology; D008297:Male; D008839:Microelectrodes; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D010656:Phenylephrine / Q000378:metabolism / Q000494:pharmacology; D010848:Picolinic Acids / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D065105:Aromatic Amino Acid Decarboxylase Inhibitors; D006834:Hydrazines; D008996:Monoamine Oxidase Inhibitors; D010848:Picolinic Acids; D015102:3,4-Dihydroxyphenylacetic Acid; D010656:Phenylephrine; C059303:lazabemide; D000499:Allylamine; D005680:gamma-Aminobutyric Acid; C040051:2-(3,4-dimethoxyphenyl)-3-fluoroallylamine; C004297:3-hydroxybenzylhydrazine; D004298:Dopamine; D006719:Homovanillic Acid