Neonatal nicotine exposure induces permanent changes in brain nicotinic receptors and behaviour in adult mice.
The effects of neonatal nicotine exposure on spontaneous and nicotine-induced behaviour in 4-month-old mice and on the development of brain nicotinic receptors were studied. The behaviour study showed that mice treated with nicotine 66 micrograms (-)nicotine base/kg body weight (bw) s.c. twice daily between 10 and 16 days postnatally displayed a hypoactive condition, whereas mice treated with saline displayed a hyperactive condition. When the nicotinic receptors in the brain cortex were analyzed, the displacement curves for [3H]nicotine(-)nicotine revealed an almost equal proportion of high- and low-affinity binding sites in 17-day-old mice, while the high-affinity sites predominated in 4-month-old mice, with affinity constants for both high- and low-affinity binding sites 10 times higher in 4-month-old mice than in 17-day-old-mice. A decrease in the number of nicotinic receptors was observed from day 17 to 4 months, mainly of the low-affinity nicotinic type. Interestingly, the displacement curves in neonatally nicotine-treated mice showed only one population of high-affinity binding sites in 17-day- and 4-month-old mice though the total binding sites in 4-month-old mice were the same for the neonatally nicotine-treated and saline-treated mice. These results indicate that neonatal nicotine treatment prevents the development of low-affinity nicotinic sites in the brain and this earlier exposure to nicotine induces a different behaviour response in adult animals to a test dose of nicotine. Days 10-16 postnatally appear to be a critical period for the effects of nicotine on the brain.
Nordberg
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Department of Pharmacology, Uppsala University, Sweden.
Zhang
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XA
Fredriksson
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A
Eriksson
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P
D000375:Aging / Q000187:drug effects*; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001921:Brain / Q000187:drug effects*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects*; D009538:Nicotine / Q000633:toxicity*; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors
D011978:Receptors, Nicotinic; D009538:Nicotine