The effects of administration of monoamine oxidase‐B inhibitors on rat striatal neurone responses to dopamine

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Abstract
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.

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