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Increased susceptibility to adult paraoxon exposure in mice neonatally exposed to nicotine
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Evolutionary Biology, Environmental Toxicology.
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Evolutionary Biology, Environmental Toxicology.
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Evolutionary Biology, Environmental Toxicology.
2004 (English)In: Toxicological Sciences, ISSN 1096-6080, E-ISSN 1096-0929, Vol. 82, no 2, 555-561 p.Article in journal (Refereed) Published
Abstract [en]

Low-dose exposure of neonatal mice to nicotine has earlier been shown to induce an altered behavioral response to nicotine in adulthood. Organophosphorus insecticides are known to affect the cholinergic system by inhibition of acetylcholinesterase. This study was undertaken to investigate whether neonatal exposure to nicotine makes mice more susceptible to a known cholinergic agent. Neonatal, 10-day-old, male mice were exposed to nicotine-base (33 microg/kg body weight) or saline s.c. twice daily on five consecutive days. At 5 months of age the animals were exposed to paraoxon (0.17 or 0.25 mg/kg body weight [29% and 37% inhibition of cholinesterase, respectively]) or saline sc every second day for 7 days. Before the first paraoxon injection, the animals were observed for spontaneous motor behavior. The spontaneous motor behavior test did not reveal any differences in behavior between the treatment groups. Immediately after the spontaneous behavior test, the animals received the first injection of paraoxon and were observed for acute effects of paraoxon on spontaneous motor behavior. The acute response to paraoxon in the spontaneous motor behavior test was a decreased level of activity in mice neonatally exposed to nicotine. Control animals showed no change in activity. Two months after the paraoxon treatment, the animals were again tested for spontaneous motor behavior. Animals neonatally exposed to nicotine and exposed to paraoxon as adults showed a deranged spontaneous motor behavior, including hyperactivity and lack of habituation.

Place, publisher, year, edition, pages
2004. Vol. 82, no 2, 555-561 p.
Keyword [en]
Animals, Animals; Newborn/*physiology, Behavior; Animal/drug effects, Cholinesterase Inhibitors/*toxicity, Cholinesterases/metabolism, Habituation (Psychophysiology)/drug effects, Insecticides/*toxicity, Male, Mice, Motor Activity/drug effects, Nicotine/*pharmacology, Nicotinic Agonists/*pharmacology, Paraoxon/*toxicity, Receptors; Muscarinic/drug effects, Receptors; Nicotinic/drug effects, Research Support; Non-U.S. Gov't
National Category
Natural Sciences
URN: urn:nbn:se:uu:diva-91052DOI: 10.1093/toxsci/kfh274PubMedID: 15356346OAI: oai:DiVA.org:uu-91052DiVA: diva2:163634
Available from: 2003-11-11 Created: 2003-11-11 Last updated: 2013-05-21Bibliographically approved
In thesis
1. Neurotoxic Effects of Nicotine During Neonatal Brain Development: Critical Period and Adult Susceptibility
Open this publication in new window or tab >>Neurotoxic Effects of Nicotine During Neonatal Brain Development: Critical Period and Adult Susceptibility
2003 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

This thesis examined neurotoxic effects of nicotine exposure during a defined critical period of neonatal brain development in mice.

In our environment there are numerous hazardous contaminants that an individual can be exposed to during its entire lifetime. In many mammalian species the neonatal period is characterised by a rapid development of the brain. The present studies have identified a defined critical period during the neonatal brain development in mice, where exposure to low doses of nicotine causes permanent disturbances in the cholinergic nicotinic receptors and altered behaviour response to nicotine at adult age. This adult reaction to nicotine, a hypoactive response, was the opposite of that observed in control animals and animals exposed to nicotine before or after this period. Animals showing a hypoactive response to nicotine lacked nicotinic low affinity binding sites in the cerebral cortex. Furthermore, neonatal exposure to nicotine affected learning and memory in adult animals, an effect that was time-dependent. This thesis also showed that neonatal exposure to nicotine increased adult susceptibility to a repeated exposure of nicotine, manifested as an even more pronounced effect in spontaneous behaviour after challenging doses of nicotine. In these animals the nicotinic receptors in the cerebral cortex, assayed by a-bungarotoxin, was decreased.

Neonatal exposure to nicotine was also shown to increase adult susceptibility to the organophosphate paraoxon, a known cholinergic agent, and to the brominated flame retardant 2,2´,4,4´,5-pentabromodiphenyl ether, a novel environmental agent, at adult age. This was seen at doses that did not affect behaviour in control animals, and was manifested as deranged spontaneous behaviour and reduced habituation, aberrations that also worsened with age.

The results indicate that differences in adult susceptibility to environmental pollutants are not necessarily an inherited condition. Rather they may well be acquired by low dose exposure to toxic agents during early life.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2003. 48 p.
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Science and Technology, ISSN 1104-232X ; 907
Biology, nicotine, neonatal development, behaviour, nicotinic receptors, susceptibility, cholinergic system, paraoxon, PBDE, Biologi
National Category
Biological Sciences
urn:nbn:se:uu:diva-3770 (URN)91-554-5800-9 (ISBN)
Public defence
2003-12-05, Lindahlsalen, EBC, Norbyv. 18A, Uppsala, 09:00
Available from: 2003-11-11 Created: 2003-11-11Bibliographically approved

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