| 1. |
- Besson, M, et al.
(författare)
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Long-term effects of chronic nicotine exposure on brain nicotinic receptors
- 2007
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 104:19, s. 8155-8160
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Tidskriftsartikel (refereegranskat)abstract
- Chronic nicotine exposure results in long-term homeostatic regulation of nicotinic acetylcholine receptors (nAChRs) that play a key role in the adaptative cellular processes leading to addiction. However, the relative contribution of the different nAChR subunits in this process is unclear. Using genetically modified mice and pharmacological manipulations, we provide behavioral, electrophysiological, and pharmacological evidence for a long-term mechanism by which chronic nicotine triggers opposing processes differentially mediated by β2*- vs. α7*nAChRs. These data offer previously undescribed insights into the understanding of nicotine addiction and the treatment of several human pathologies by nicotine-like agents chronically acting on β2*- or α7*nAChRs.
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| 2. |
- Cohen, G, et al.
(författare)
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beta 2 nicotinic acetylcholine receptor subunit modulates protective responses to stress: A receptor basis for sleep-disordered breathing after nicotine exposure
- 2002
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 99:20, s. 13272-13277
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Tidskriftsartikel (refereegranskat)abstract
- Nicotine exposure diminishes the protective breathing and arousal responses to stress (hypoxia). By exacerbating sleep-disordered breathing, this disturbance could underpin the well established association between smoking and the increased risk of sudden infant death syndrome. We show here that the protective responses to stress during sleep are partially regulated by particular nicotinic acetylcholine receptors (nAChRs). We compared responses of sleeping wild-type and mutant mice lacking the β2 subunit of the nAChR to episodic hypoxia. Arousal from sleep was diminished, and breathing drives accentuated in mutant mice indicating that these protective responses are partially regulated by β2-containing nAChRs. Brief exposure to nicotine significantly reduced breathing drives in sleeping wild-type mice, but had no effect in mutants. We propose that nicotine impairs breathing (and possibly arousal) responses to stress by disrupting functions normally regulated by β2-containing, high-affinity nAChRs.
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| 3. |
- Cohen, G, et al.
(författare)
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Perinatal exposure to nicotine causes deficits associated with a loss of nicotinic receptor function
- 2005
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Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 102:10, s. 3817-3821
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 4. |
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| 6. |
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| 7. |
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| 8. |
- Lagercrantz, H, et al.
(författare)
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Basic consciousness of the newborn
- 2010
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Ingår i: Seminars in perinatology. - : Elsevier BV. - 1558-075X .- 0146-0005. ; 34:3, s. 201-206
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Tidskriftsartikel (refereegranskat)
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