Neurobehavioural defects in adult mice neonatally exposed to nicotine: changes in nicotine-induced behaviour and maze learning performance

Neonatal exposure to low doses of nicotine has been shown to disturb the de velopment of low-affinity nicotinic binding sites in the cerebral cortex an d to elicit a deviant behavioural response to nicotine in adult mice. In th is study, 10-day-old male NMRI mice were exposed to one of three different doses of nicotine (3.3, 33, or 66 mug nicotine-base/kg body wt.) s.c. twice daily on 5 consecutive days to study dose-response effects of nicotine on adult spontaneous and nicotine-induced motor behaviour. The nicotine-induce d behaviour test revealed a hypoactive response to nicotine in 4-month-old mice neonatally exposed to 33 or 66 mug nicotine-base, whereas the response to nicotine in control animals and mice exposed to 3.3 mug nicotine-base w as an increased activity. Learning and memory functions were also investiga ted in adult animals neonatally exposed to 66 tg nicotine-base/kg body wt. in the same manner, in the Morris water maze and in the Radial arm maze. In the swim maze and the Radial arm maze tests, no significant differences we re observed between nicotine-treated and control animals at the age of 4 mo nths. At 7 months, however, a significant difference in performance was evi dent, indicating a time-response/time-dependent effect. Furthermore, it was shown that in mice exposed neonatally to a nicotine dose known to inhibit the development of the nicotinic low affinity-binding site (LA), the respon se to nicotine could not cause any increase in spontaneous motor activity a s seen in controls. (C) 2001 Elsevier Science B.V. All rights reserved.