{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T01:09:47Z","timestamp":1788397787891,"version":"build-2803163510"},"reference-count":241,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T00:00:00Z","timestamp":1759708800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Behav. Neurosci."],"abstract":"<jats:p>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\u2019 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 <jats:italic>bona fide<\/jats:italic> co-transmitter effects of these metabolites in future work.<\/jats:p>","DOI":"10.3389\/fnbeh.2025.1537975","type":"journal-article","created":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T06:08:56Z","timestamp":1759730936000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Nitrogen waste metabolism as a locus of nitrergic co-transmission in the brain"],"prefix":"10.3389","volume":"19","author":[{"given":"Joseph L.","family":"Bedont","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,10,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"R1","DOI":"10.1016\/S0014-2999(98)00089-2","article-title":"Nitric oxide mediates mecamylamine- and naloxone-precipitated nicotine withdrawal.","volume":"345","author":"Adams","year":"1998","journal-title":"Eur. 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