Perinatal Exposure to Nicotine Causes Deficits Associated with a Loss of Nicotinic Receptor Function

We investigated the role played by β2-containing neuronal nicotinic receptors [nicotinic acetylcholine receptors (nAChRs)] in mediating nicotine's side effects in the fetus and newborn. Pregnant WT and mutant mice lacking the β2 nAChR subunit were implanted with osmotic minipumps that delivered...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2005-03, Vol.102 (10), p.3817-3821
Main Authors: Cohen, Gary, Roux, Jean-Christophe, Grailhe, Régis, Malcolm, Girvan, Changeux, Jean-Pierre, Lagercrantz, Hugo
Format: Article
Language:English
Subjects:
Animals
Arousal
Arousal - drug effects
Biological Sciences
Biosynthesis
Brain hypoxia
Breathing
Catecholamines
Catecholamines - biosynthesis
Female
Fetus
Fetus - drug effects
Genotypes
Hypoxia
Life Sciences
Male
Medicin och hälsovetenskap
Mice
Mice, Inbred C57BL
Neurobiology
Neurology
Neurons and Cognition
Nicotine
Nicotine - toxicity
Pregnancy
Prenatal development
Receptors
Receptors, Nicotinic
Receptors, Nicotinic - drug effects
Receptors, Nicotinic - physiology
Respiration
Respiration - drug effects
Rodents
Side effects
Tobacco smoking
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Summary:We investigated the role played by β2-containing neuronal nicotinic receptors [nicotinic acetylcholine receptors (nAChRs)] in mediating nicotine's side effects in the fetus and newborn. Pregnant WT and mutant mice lacking the β2 nAChR subunit were implanted with osmotic minipumps that delivered either water or a controlled dose of nicotine. Subsequently, we compared the development of the sympathoadrenal system and breathing and arousal reflexes of offspring shortly after birth, a period of increased vulnerability to nicotine exposure. Newborn WT pups exposed to nicotine exhibited all of the deficits associated with maternal tobacco and nicotine use, and linked to poor neonatal outcome: growth restriction, unstable breathing, and impaired arousal and catecholamine biosynthesis. Remarkably similar deficits were detected in pups lacking β2-containing nAChRs. Loss-of-function of these nAChRs consequently reproduces with astonishing fidelity many of the abnormalities caused by perinatal nicotine exposure. We propose that the underlying mechanisms of nicotine's detrimental side effects on a range of crucial defensive reflexes involve loss of function of nAChR subtypes, possibly via activity-dependent desensitization.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0409782102