Exposure to nicotine during a defined period in neonatal life induces permanent changes in brain nicotinic receptors and in behaviour of adult mice

Abstract

Neonatal exposure to low doses of nicotine has been shown to prevent the development of low-affinity nicotine-binding sites, and to elicit a different behaviour response to nicotine in the mice as adults. This study has identified a defined period during the development of neonatal mouse brain for the induction of these permanent changes. Neonatal mice, aged either 3, 10, or 19 days were exposed to nicotine, 66 μg nicotine-base/kg b.wt., s.c. twice daily, on 5 consecutive days. In the cerebral cortex, high- and low-affinity (HA and LA) nicotine-binding sites were assayed ( 3 H -nicotine/nicotine) in neonatal male mice aged 8, 15, and 24 days and in adult mice aged 4 months. Spontaneous behaviour and nicotine-induced behaviour were observed in 4-month-old male mice. The spontaneous behaviour test did not indicate any difference between saline- and nicotine-treated mice, whereas the nicotine-induced behaviour test revealed a hypoactive response to nicotine, though only in mice given nicotine on days 10–14. The response of controls and the other age categories to nicotine was an increased activity. At no time during the neonatal period could LA nicotine-binding sites be found following nicotine treatment, but the persistence of this effect was evident only in adult mice exposed on days 10–14.