title: Prenatal nicotine exposure increases hyperventilation in α4-knock-out mice during mild asphyxia.
abstract: Prenatal nicotine exposure alters breathing and ventilatory responses to stress through stimulation of nicotine acetylcholine receptors (nAChRs). We tested the hypothesis that α4-containing nAChRs are involved in mediating the effects of prenatal nicotine exposure on ventilatory and metabolic responses to intermittent mild asphyxia (MA). Using open-flow plethysmography, we measured ventilation (V̇(E)) and rate of O2 consumption ( V̇(O2)) of wild-type (WT) and α4-knock-out (KO) mice, at postnatal (P) days 1-2 and 7-8, with and without prenatal nicotine exposure (6 mg kg(-1) day(-1) beginning on embryonic day 14). Mice were exposed to seven 2 min cycles of mild asphyxia (10% O2 and 5% CO2), each interspersed with 2 min of air. Compared to WT, α4 KO mice had increased air V̇(E) and V̇(O2) at P7-8, but not P1-2. Irrespective of age, genotype had no effect on the hyperventilatory response (increase in V̇(E)/V̇(O2)) to MA. At P1-2, nicotine suppressed air V̇(E) and V̇(O2) in both genotypes but did not affect the hyperventilatory response to MA. At P7-8 nicotine suppressed air V̇(E) and V̇(O2) of only α4 KO's but also significantly enhanced V̇(E) during MA (nearly double that of WT; p<0.001). This study has revealed complex effects of α4 nAChR deficiency and prenatal nicotine exposure on ventilatory and metabolic interactions and responses to stress.
authors.affiliation: Department of Zoology, Latrobe University, Melbourne, VIC 3086, Australia. Electronic address: J.Avraam@alfred.org.au.
authors.forename: Joanne
authors.initials: J
authors.lastname: Avraam
authors.affiliation: Department of Women & Child Health, Neonatal Unit, Karolinska Institute, Elevhemmet H1:02 S171-76, Stockholm, Sweden.
authors.forename: Gary
authors.initials: G
authors.lastname: Cohen
authors.affiliation: Florey Institute of Neuroscience and Mental Health, 30 Royal Parade, Parkville, VIC 3052, Australia.
authors.forename: John
authors.initials: J
authors.lastname: Drago
authors.affiliation: Department of Zoology, Latrobe University, Melbourne, VIC 3086, Australia; Adaptational and Evolutionary Respiratory Physiology Laboratory, School of Zoology, Hobart, TAS, Australia.
authors.forename: Peter B
authors.initials: PB
authors.lastname: Frappell
mesh_terms: D000818:Animals; D005260:Female; D008297:Male; D051379:Mice; D011247:Pregnancy; D000367:Age Factors; D000704:Analysis of Variance; D000831:Animals, Newborn; D001238:Asphyxia Neonatorum / Q000503:physiopathology; D006985:Hyperventilation / Q000139:chemically induced / Q000235:genetics; D018345:Mice, Knockout; D010101:Oxygen Consumption / Q000187:drug effects / Q000235:genetics; D011297:Prenatal Exposure Delayed Effects / Q000235:genetics / Q000503:physiopathology; D011978:Receptors, Nicotinic / Q000172:deficiency / Q000235:genetics; D012119:Respiration / Q000187:drug effects / Q000235:genetics; D013990:Tidal Volume / Q000187:drug effects / Q000235:genetics; D013997:Time Factors; D001724:Birth Weight
chemical_list: D011978:Receptors, Nicotinic
keywords: Alpha-4 nicotine receptor subunit; Asphyxia; Hyperventilation; Knock-out mouse; Nicotine; Ventilation