BEHAVIORAL-EFFECTS OF SMOKELESS TOBACCO ON THE NEONATE AND YOUNG SPRAGUE-DAWLEY RAT

Three dosages of Smokeless Tobacco (ST) extract were given to pregnant Sprague-Dawley rats by oral gavage on gestational days (GD) 6-20. The three dosages contained ST extract equivalent to 1.33 mg/kg nicotine (STD-1), 4.0 mg/kg nicotine (STD-2), and 6.0 mg/kg nicotine (STD-3). D ams were intubated three times per day at 8 a.m., 11 a.m., and 2 p.m., providing total daily ST dosages of 4 mg/kg, 12 mg/kg, and 18 mg/kg, respectively. Controls received equivalent volumes of water by gavage. Dams were allowed to deliver, and all biological mothers raised their own pups. On postnatal day 1 (PND 1), litters were culled to 4 +/- 1 females and 4 +/- 1 males. Weights, physical landmark development, and behavioral performance of pups were monitored during pre- and post-we aning periods. Behavioral tests included surface righting, negative ge otaxis, swimming development, open field activity, and active avoidanc e in shuttle box. Our results show that the two higher doses resulted in reduced maternal weight gain. During the pre-weaning period, signif icant pup weight reductions were noted in the STD-2 pups until PND6, a nd in the STD-3 group until PND15. In the STD-1 group no statistically significant weight reduction was noted on PNDs 1 and 3, but starting with PND6, pup weights surpassed control group weights. This weight di fference persisted throughout the post-weaning period also (P < .05 on PND30 and PND42). The STD-3 pup weights continued to be consistently and significantly (P < .05) reduced throughout the post-weaning period (except on PND24); likewise, the STD-2 pups continued to have lower w eights, but at a significant level P < .05) on PND30 only. The incide nce of deaths was increased in a dose-related manner. No significant d ifferences were noted for pinna detachment and incisor erpton; however ST-treatment was significant in affecting earlier eye opening and vag inal patency. N significant ST treatment effects were seen on netive g eotaxis, but for surface righting a decreasedsuccess rate was noted fo r the ST-treated groups. Significant differences were noted in swimmin g development, with the STD-2 pups performing best. Open field activit y, as expected, increased from the preweaning to post-weaning periods. During the pre weaning period the STD-3 pups were more active, and du ring post-weaning, the STD-1 pups were more active, but no differences were noted in vertical activity or in the number of stereotypical mov ements. No treatment-related differences were noted in the active avoi dance shuttle box. We conclude that at high doses ST reduces pre-and p ost-weaning offspring weight gain and increases fetal mortality. ST at the low dose appears to have the opposite effect, in that these offsp ring weights actually exceed control weights. ST also alters activity levels and swimming development, while no differences are noted in the rats' performance in active avoidance tests on learning. Therefore, S T exposure during the embryonic and fetal stages of rat development pr oduces developmental toxicity and suggests that its effects may be com parable to results observed by other investigators using smoked tobacc o. (C) 1994 Wiley-Liss, Inc.