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The effects of administration of monoamine oxidase‐B inhibitors on rat striatal neurone responses to dopamine
Author(s) -
Berry M.D.,
Scarr E.,
Zhu M.Y.,
Paterson I.A.,
Juorio A.V.
Publication year - 1994
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1994.tb17119.x
Subject(s) - homovanillic acid , dopamine , neurochemical , dopaminergic , monoamine oxidase , chemistry , endocrinology , medicine , monoamine neurotransmitter , nigrostriatal pathway , pargyline , 3,4 dihydroxyphenylacetic acid , monoamine oxidase b , pharmacology , serotonin , biology , biochemistry , substantia nigra , enzyme , receptor
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 γ 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 homo vanillic 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 1 ‐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.