Abstract
The activity of monoamine oxidases (MAOs) in the brain is often associated with neurodegenerative diseases. The study of MAOs in vivo or ex vivo is generally performed using MAO inhibitors and rarely using substrates. We present a pharmacological approach using intracerebral microdialysis to study the activity of MAO in the striatum and the prefrontal cortex of rats. It consists of applying ascending concentrations of 3-methoxytyramine (3-MT) as a substrate via the probes and measuring the indirect product homovanillic acid generated by MAO activity. We present herein the methodologies comprising our in-house stereotaxic procedures in rats, the microdialysis perfusion system and the substrate application, and the neurochemical analysis of the samples.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Ma J, Yoshimura M, Yamashita E, Nakagawa A, Ito A, Tsukihara T (2004) Structure of rat monoamine oxidase a and its specific recognitions for substrates and inhibitors. J Mol Biol 338:103–114
Binda C, Li M, Hubalek F, Restelli N, Edmondson DE, Mattevi A (2003) Insights into the mode of inhibition of human mitochondrial monoamine oxidase B from high-resolution crystal structures. Proc Natl Acad Sci U S A 100:9750–9755
Binda C, Wang J, Pisani L, Caccia C, Carotti A, Salvati P, Edmondson DE, Mattevi A (2007) Structures of human monoamine oxidase B complexes with selective noncovalent inhibitors: safinamide and coumarin analogs. J Med Chem 50:5848–5852
Finberg JP (2014) Update on the pharmacology of selective inhibitors of MAO-A and MAO-B: focus on modulation of CNS monoamine neurotransmitter release. Pharmacol Ther 143:133–152
Chagraoui A, Boulain M, Juvin L, Anouar Y, Barriere G, Deurwaerdere P (2019) L-DOPA in Parkinson's disease: looking at the “false” neurotransmitters and their meaning. Int J Mol Sci 21:294
De Deurwaerdere P, Di Giovanni G (2017) Serotonergic modulation of the activity of mesencephalic dopaminergic systems: therapeutic implications. Prog Neurobiol 151:175–236
Di Chiara G (1990) In-vivo brain dialysis of neurotransmitters. Trends Pharmacol Sci 11:116–121
De Deurwaerdere P, Bonhomme N, Le Moal M, Spampinato U (1995) D-fenfluramine increases striatal extracellular dopamine in vivo independently of serotonergic terminals or dopamine uptake sites. J Neurochem 65:1100–1108
De Deurwaerdere P, Bonhomme N, Lucas G, Le Moal M, Spampinato U (1996) Serotonin enhances striatal dopamine outflow in vivo through dopamine uptake sites. J Neurochem 66:210–215
De Deurwaerdere P, Di Giovanni G, Millan MJ (2017) Expanding the repertoire of L-DOPA's actions: a comprehensive review of its functional neurochemistry. Prog Neurobiol 151:57–100
Paxinos G, Watson C (2007) The rat brain in stereotaxic coordinates, 6th edn. Academic Press, San Diego
Bonhomme N, De Deurwaerdere P, Le Moal M, Spampinato U (1995) Evidence for 5-HT4 receptor subtype involvement in the enhancement of striatal dopamine release induced by serotonin: a microdialysis study in the halothane-anesthetized rat. Neuropharmacology 34:269–279
Moghaddam B, Bunney BS (1989) Ionic composition of microdialysis perfusing solution alters the pharmacological responsiveness and basal outflow of striatal dopamine. J Neurochem 53:652–654
Navailles S, Lagiere M, Contini A, De Deurwaerdere P (2013) Multisite intracerebral microdialysis to study the mechanism of L-DOPA induced dopamine and serotonin release in the parkinsonian brain. ACS Chem Neurosci 4:680–692
Lucas G, De Deurwaerdere P, Caccia S, Umberto S (2000) The effect of serotonergic agents on haloperidol-induced striatal dopamine release in vivo: opposite role of 5-HT(2A) and 5-HT(2C) receptor subtypes and significance of the haloperidol dose used. Neuropharmacology 39:1053–1063
Miguelez C, Navailles S, Delaville C, Marquis L, Lagiere M, Benazzouz A, Ugedo L, De Deurwaerdere P (2016) L-DOPA elicits non-vesicular releases of serotonin and dopamine in hemiparkinsonian rats in vivo. Eur Neuropsychopharmacol 26:1297–1309. https://doi.org/10.1016/j.euroneuro.2016.05.004
De Deurwaerdere P, Binda C, Corne R, Leone C, Valeri A, Valoti M, Ramsay RR, Fall Y, Marco-Contelles J (2017) Comparative analysis of the neurochemical profile and MAO inhibition properties of N-(Furan-2-ylmethyl)-N-methylprop-2-yn-1-amine. ACS Chem Neurosci 8:1026–1035
Acknowledgments
This project was initiated via collaborations between members of the COST Action CM1103, “Structure-based drug design for diagnosis and treatment of neurological diseases.” It received additional support from the Idex Bordeaux and the Centre National de la Recherche Scientifique (P. De Deurwaerdère; PEPS IDEX project 2013).
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2023 The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature
About this protocol
Cite this protocol
De Deurwaerdère, P., Samb, N., El Boukhari, H., Corne, R., Chagraoui, A., Di Giovanni, G. (2023). In Vivo Study of Monoamine Oxidases Using Multisite Intracerebral Microdialysis. In: Binda, C. (eds) Monoamine Oxidase. Methods in Molecular Biology, vol 2558. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-2643-6_14
Download citation
DOI: https://doi.org/10.1007/978-1-0716-2643-6_14
Published:
Publisher Name: Humana, New York, NY
Print ISBN: 978-1-0716-2642-9
Online ISBN: 978-1-0716-2643-6
eBook Packages: Springer Protocols