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

Abstract

(−)−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. 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. 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). 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. Neurochemical analysis revealed this to occur at a dose of NSD 1015 (10 mg kg−1) selective for reduction of elevated PE levels. 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. 1994 British Pharmacological Society