LAUSR

Perinatal 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 ePet-EYFP mice. 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 SIDS.