REVIEW article
Front. Behav. Neurosci.
Sec. Motivation and Reward
Volume 19 - 2025 | doi: 10.3389/fnbeh.2025.1537975
This article is part of the Research TopicNeurotransmitter Corelease and its Impact on Neurocircuits and DiseaseView all articles
Nitrogen waste metabolism as a locus of nitrergic co-transmission in the brain
Provisionally accepted
- Kent State University, Kent, United States
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Nitrogen detoxification pathways in the central nervous system supply a range of neurotransmitters, ranging from long-appreciated examples like nitric oxide and agmatine, to emergent neurotransmitters including spermidine, spermine, and polyamine-derived GABA. This review summarizes specialized nitrogen detoxification pathways in the brain, and evidence supporting several of these pathways' metabolites as co-transmitters in neurons and glia. Known functional roles of these nitrergic co-transmitters in learning, sleep, addiction, and other neurological disorders will be discussed to elucidate the adaptive value of nitrergic co-transmission, with a particular focus on nitrergic modulation of coincidence detection at NMDA receptors. Finally, this review sums up with a discussion of how nitrogen homeostasis in the brain serves as a coordinating locus for the control of these nitrergic neurotransmitters, and approaches for identifying bona fide co-transmitter effects of these metabolites in future work.
Keywords: Nitric Oxide, Polyamines, polyamine-derived GABA, Metabolism, Behavior, Sleep, Addiction, Learning
Received: 02 Dec 2024; Accepted: 10 Sep 2025.
Copyright: © 2025 Bedont. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Joseph Bedont, jbedont@kent.edu
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