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Direct and decarboxylation-dependent effects of neurotransmitter precursors on firing of isolated monoaminergic neurons

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Abstract

To elucidate mechanisms that underlie the profound physiological effects of the monoamine precursors 5-hydroxy-l-tryptophan (5-HTP) and l-3,4-dihydroxyphenylalanine (l-DOPA), we examined their action on single monoaminergic neurons isolated from the ganglia of the gastropod snail Lymnaea stagnalis. In isolated serotonergic PeA motoneurons, 5-HTP produced excitation. The effect was mimicked by serotonin at 0.5–1 μM, masked by pretreatment with serotonin at higher concentrations, and abolished by the inhibitor of aromatic amino acid decarboxylase (AAAD) m-hydroxybenzylhydrazine (NSD-1015), the inhibitor of the vesicular monoamine transporter reserpine or the serotonin receptor antagonist mianserin. Exposure of the dopaminergic interneurons RPeD1 to l-DOPA caused a biphasic effect composed of a depolarization followed by a hyperpolarization. AAAD inactivation with NSD-1015, as well as the blockade of dopamine receptors with sulpiride, resulted in the enhancement of the excitatory effect, and the abolition of the inhibitory effect. Dopamine caused hyperpolarization and masked the inhibitory phase of l-DOPA action. The results show that precursors affect the rate of firing of isolated monoaminergic neurons and that their effect is completely or partially mediated by the enhanced synthesis of the respective neurotransmitter, followed by extrasynaptic release of the latter and activation of extrasynaptic autoreceptors.

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Abbreviations

5-HTP:

5-hydroxy-l-tryptophan

l-DOPA:

l-3,4-dihydroxyphenylalanine

AAAD:

Aromatic amino acid decarboxylase

NSD-1015:

m-hydroxybenzylhydrazine

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Acknowledgments

This work was supported by grant RFBR 05-04-49812 and 08-04-00120 (D.A.S.). Personal support was provided to V.E.D. from the Science Support Foundation.

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Authors and Affiliations

  1. Laboratory of Comparative Physiology, Institute of Developmental Biology of the Russian Academy of Sciences, Vavilov Str. 26, 119991, Moscow, Russia

    Varvara E. Dyakonova, Ilya A. Chistopolsky, Taisia L. Dyakonova, Dmitry D. Vorontsov & Dmitri A. Sakharov

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  1. Varvara E. Dyakonova
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  2. Ilya A. Chistopolsky
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  3. Taisia L. Dyakonova
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  4. Dmitry D. Vorontsov
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  5. Dmitri A. Sakharov
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Correspondence to Varvara E. Dyakonova.

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Dyakonova, V.E., Chistopolsky, I.A., Dyakonova, T.L. et al. Direct and decarboxylation-dependent effects of neurotransmitter precursors on firing of isolated monoaminergic neurons. J Comp Physiol A 195, 515–527 (2009). https://doi.org/10.1007/s00359-009-0428-5

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  • DOI: https://doi.org/10.1007/s00359-009-0428-5

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