Effects of maternal intravenous nicotine administration on locomotor behavior in pre-weanling rats

Abstract

Maternal tobacco use is associated with adverse developmental outcomes in offspring, including hyperactivity. Animal studies attempting to model this phenomenon have primarily used continuous s.c. nicotine infusion as the method of nicotine administration, which does not model the intermittent bolus delivery of nicotine associated with smoking in humans. The purpose of the present experiment was to examine the locomotor activity of pre-weanling offspring of pregnant rats exposed to an i.v. nicotine dosing protocol that approximates the pattern of nicotine exposure in moderate to heavy smokers. Pregnant rats were administered an i.v. bolus of 0.03 mg/kg nicotine (N=13) or saline (N=10) every 14 min for 16 hr/day, resulting in a total daily dose of 2 mg/kg (base), from gestational day 4 to delivery. Pups from each litter were tested for spontaneous locomotor activity on postnatal days (PND) 19-21 and nicotine-induced locomotor activity on PND 22. Mean birth weight was significantly lower in nicotine-exposed pups compared to controls, but body weights were equivalent between groups by the time of behavioral testing. Mean total distance traveled, vertical counts, and stereotypy counts were lower on PND 19 in nicotine-exposed pups compared to controls, but only the difference in mean stereotypy counts was statistically significant. Within session analysis revealed that both distance traveled and stereotypy were significantly decreased in nicotine-exposed pups in the first five minutes of the session on PND 19. Total time spent in the center of the field was also lower in nicotine exposed pups. Nicotine-induced increases in activity on PND 22 did not differ according to gestational exposure. These findings demonstrate that prenatal nicotine exposure in a model that mimics the pattern of nicotine exposure from cigarette smoking in humans results in offspring that exhibit low birth weight and hypoactivity in a novel environment.

Developmental nicotine exposure induced alterations in behavior and glutamate receptor function in hippocampus

“…Our results indicate that prenatal nicotine exposure results in elevated anxiety and depression in the young rat offspring. These results are in agreement with that of a recent study [63] that reported open-field hypoactivity in gestational nicotine-exposed rats. Other reports have also shown the presence of anxiety with elevated plus-maze test in older adolescent rats being about 40 days old [17,21].…”

Methylphenidate Enhances the Abuse-Related Behavioral Effects of Nicotine in Rats: Intravenous Self-Administration, Drug Discrimination, and Locomotor Cross-Sensitization

“…Consistent with other reports LeSage et al, 2006), the results of the locomotor activity experiment revealed that nicotine initially induced hypoactivity, followed by hyperactivity across repeated injections. More important, although there was little evidence indicative of cross-sensitization to the initial methylphenidate challenge following nicotine exposure, nicotine pre-exposure promoted the induction of locomotor sensitization following three repeated methylphenidate injections.…”

Disentangling prenatal and inherited influences in humans with an experimental design

“…Our findings for prenatal smoking and birth weight concur with results from experimental animal studies (10,11,24) and studies of naturally conceived children (15). The existing literature for prenatal smoking and offspring antisocial behavior is less clear than that for birth weight, highlighting the need for novel designs in this area.…”

“…Consider the example of smoking in pregnancy, which is associated with a number of adverse outcomes in offspring including reduced birth weight and increased antisocial behavior. Plausible physiological mechanisms have been suggested to explain these associations (8)(9)(10)(11). However, smoking in pregnancy is influenced by maternal characteristics as well as by maternal genotype (6,8,12).…”

“…Individuals who are antisocial as children show a range of social and achievement impairments and increased rates of crime in adult life (14). Studies of animals (10,11) and epidemiological cohorts (15) suggest that tobacco smoking during pregnancy likely has a causal risk effect on reduced birth weight. There is uncertainty about why there are links between maternal smoking during pregnancy and offspring antisocial behavior, both of which are heritable phenotypes (12,16).…”