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 development of low-affinity nicotinic binding sites in the cerebral cortex and to elicit a deviant behavioural response to nicotine in adult mice. In this study, 10-day-old male NMRI mice were exposed to one of three different doses of nicotine (3.3, 33, or 66 microg 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-induced behaviour test revealed a hypoactive response to nicotine in 4-month-old mice neonatally exposed to 33 or 66 microg nicotine-base, whereas the response to nicotine in control animals and mice exposed to 3.3 microg nicotine-base was an increased activity. Learning and memory functions were also investigated in adult animals neonatally exposed to 66 microg 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 were observed between nicotine-treated and control animals at the age of 4 months. At 7 months, however, a significant difference in performance was evident, 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 response to nicotine could not cause any increase in spontaneous motor activity as seen in controls.
Ankarberg
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E
Evolutionary Biology Center, Department of Environmental Toxicology, Uppsala University, Norbyv.18A, S-752 36 Uppsala, Sweden. emma.ankarberg@ebc.uu.se
Fredriksson
A
A
Eriksson
P
P
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001143:Arousal / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004924:Escape Reaction / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D011939:Mental Recall / Q000187:drug effects; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects*; D009538:Nicotine / Q000494:pharmacology*; D011340:Problem Solving / Q000187:drug effects; D011978:Receptors, Nicotinic / Q000187:drug effects
D011978:Receptors, Nicotinic; D009538:Nicotine