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ToxSci Advance Access published online on September 8, 2004
Toxicological Sciences, doi:10.1093/toxsci/kfh274
Toxicological Sciences © Society of Toxicology 2004; all rights reserved
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Received May 27, 2004
Accepted August 31, 2004

Neurotoxicology

Increased Susceptibility to Adult Paraoxon Exposure in Mice Neonatally Exposed to Nicotine

Emma Ankarberg 1*, Anders Fredriksson 1, and Per Eriksson 1

1 Department of Environmental Toxicology, Uppsala University, Norbyvägen 18A, SE-752 36 Uppsala, Sweden

* To whom correspondence should be addressed. E-mail: emma.ankarberg{at}ebc.uu.se.


  Abstract

Low dose exposure of neonatal mice to nicotine has earlier been shown to induce an altered behavioural 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 µg/kg b.wt.) or saline s.c. twice daily on 5 consecutive days. At five months of age the animals were exposed to paraoxon (0.17 or 0.25 mg/kg b.wt. (29% and 37% inhibition of cholinesterase, respectively)) or saline s.c. every second day for 7 days. Before the first paraoxon injection, the animals were observed for spontaneous motor behaviour. The spontaneous motor behaviour test did not reveal any differences in behaviour between the treatment groups. Immediately after the spontaneous behaviour test the animals received the first injection of paraoxon and were observed for acute effects of paraoxon on spontaneous motor behaviour. The acute response to paraoxon in the spontaneous motor behaviour 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 behaviour. Animals neonatally exposed to nicotine and exposed to paraoxon as adults showed a deranged spontaneous motor behaviour, including hyperactivity and lack of habituation.

Keywords: nicotine; paraoxon; development; mice; cholinergic; behaviour.
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