Metergoline, pirenperone and pizotifen alter dopamine and 5-hydroxytryptamine synthesis in discrete rat brain nuclei

The effects of the 5-hydroxytryptamine receptor antagonists metergoline, pirenperone and pizotifen on 5-hydroxytryptamine and dopamine synthesis were determined by measuring the rate of accumulation of 5-hydroxytryptamine and 3,4-dihydroxyphenylalanine, respectively, after administering l-tryptophan and m-hydroxybenzylhydrazine, an inhibitor of aromatic-l-amino acid decarboxylase. 5-Hydroxytryptophan, 3,4-dihydroxyphenylalanine and l-tryptophan were measured in four forebrain regions, the caudate putamen, nucleus accumbens, nucleus septi lateralis, and nucleus amygdaloideus centralis, which contain terminals of 5-hydroxytryptamine and dopamine neurons. Metergoline increased 5-hydroxytryptophan and 3,4-dihydroxyphenylalanine accumulation, and decreased l-tryptophan concentration in a dose- and time-dependent manner. Pirenperone increased 5-hydroxytryptophan and 3,4-dihydroxyphenylalanine accumulation, but had no effect on l-tryptophan levels. These effects of pirenperone were time- and dose-related. Finally, pizotifen increased 5-hydroxytryptophan accumulation in a dose-related and time-dependent manner, but did not alter 3,4-dihydroxyphenylalanine or l-tryptophan concentrations. All the drug effects generally occurred in all four nuclei. These results suggest that 5-hydroxytryptamine receptor antagonists may affect synthesis in 5-hydroxytryptamine and/or dopamine neurons after l-tryptophan treatment and aromatic-l-amino acid decarboxylase inhibition.