• Joanne Avraam, Yuanming Wu, and George Bradley Richerson.
• Department of Neurology, University of Iowa, Iowa City, IA 52242, United States; Melbourne School of Psychological Sciences, University of Melbourne, Melbourne, Victoria 3010, Australia.
• Neuroscience. 2020 Oct 15; 446: 80-93.

AbstractPerinatal exposure to nicotine produces ventilatory and chemoreflex deficits in neonatal mammals. Medullary 5-HT neurons are putative central chemoreceptors that innervate respiratory nuclei and promote ventilation, receive cholinergic input and express nicotinic acetylcholine receptors (nAChRs). Perforated patch clamp recordings were made from cultured 5-HT neurons dissociated from the medullary raphé of 0-3 day old mice expressing enhanced yellow fluorescent protein driven by the enhancer region for PET1 (ePet-EYFP). The effect of exposure to low (6 mg kg-1day-1) or high (60 mg kg-1day-1) doses of nicotine in utero (prenatal), in culture (postnatal), or both and the effect of acute nicotine exposure (10 μM), were examined on baseline firing rate (FR at 5% CO2, pH = 7.4) and the change in FR with acidosis (9% CO2, pH 7.2) in young (12-21 days in vitro, DIV) and older (≥22 DIV) acidosis stimulated 5-HT neurons. Nicotine exposed neurons exhibited ∼67% of the response to acidosis recorded in neurons given vehicle (p = 0.005), with older neurons exposed to high dose prenatal and postnatal nicotine, exhibiting only 28% of that recorded in the vehicle neurons (p < 0.01). In neurons exposed to low or high dose prenatal and postnatal nicotine, acute nicotine exposure led to a smaller increase in FR (∼+51% vs +168%, p = 0.026) and response to acidosis (+6% vs +67%, p = 0.014) compared to vehicle. These data show that exposure to nicotine during development reduces chemosensitivity of 5-HT neurons as they mature, an effect that may be related to the abnormal chemoreflexes reported in rodents exposed to nicotine in utero, and may cause a greater risk for sudden infant death syndrome (SIDS).Copyright © 2020 IBRO. Published by Elsevier Ltd. All rights reserved.

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