title: α4-Containing nicotinic receptors contribute to the effects of perinatal nicotine on ventilatory and metabolic responses of neonatal mice to ambient cooling.
abstract: Among numerous studies, perinatal nicotine exposure (PN) has had variable effects on respiratory control in the neonatal period. The effects of acute nicotine exposure on breathing are largely mediated by α4-containing nicotine acetylcholine receptors (nAChRs). These receptors are also involved in thermoregulatory responses induced by both acetylcholine and nicotine. We therefore hypothesized that α4-containing nAChRs would mediate the effects of PN on the metabolic and ventilatory responses of neonates to modest cold exposure. Wild-type (WT) and α4 knockout (KO) mice were exposed to 6 mg·kg-1·day-1nicotine or vehicle from embryonicday 14At postnatalday(P)7mice were cooled from an ambient temperature (TA) of 32 to 20°C. Body temperature (TB), rate of O2consumption (V̇o2), ventilation (V̇e), respiratory frequency (FB), and tidal volume (VT) were continually monitored. An absence of α4 had no effect on the metabolic response to ambient cooling. Surprisingly, PN selectively increased the metabolic response of KO pups to cooling. Regardless, KO pups became hypothermic to the same degree as WT pups, and for both genotypes the drop in TBwas exacerbated by PN. PN led to hyperventilation in WT pups caused by an increase in VT, an effect that was absent in α4 KO littermates. We show that PN interacts with α4-containing nAChRs in unique ways to modulate the control of breathing and thermoregulation in the early postnatal period.
authors: Department of Zoology, La Trobe University, Melbourne, Victoria, Australia; javraam@unimelb.edu.au.|Department of Psychological Sciences, University of Melbourne, Victoria, Australia; and.
authors: Joanne
authors: J
authors: Avraam
authors: Department of Biomedical Sciences, University of Missouri, Columbia, Missouri.
authors: Kevin J
authors: KJ
authors: Cummings
authors: Department of Zoology, La Trobe University, Melbourne, Victoria, Australia.
authors: Peter B
authors: PB
authors: Frappell
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001833:Body Temperature Regulation / Q000187:drug effects*; D003080:Cold Temperature; D004734:Energy Metabolism / Q000187:drug effects*; D004781:Environmental Exposure / Q000009:adverse effects; D005260:Female; D005731:Ganglionic Stimulants / Q000494:pharmacology / Q000633:toxicity; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009538:Nicotine / Q000494:pharmacology* / Q000633:toxicity; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000503:physiopathology*; D012123:Pulmonary Ventilation / Q000187:drug effects*; D011978:Receptors, Nicotinic / Q000378:metabolism*
chemical_list: D005731:Ganglionic Stimulants; D011978:Receptors, Nicotinic; D009538:Nicotine
keywords: breathing; neonate; nicotine; nicotinic receptor; thermogenesis