Behavioral effects of prenatally administered smokeless tobacco on rat offspring.
Two dosages of Smokeless Tobacco (ST) extract were given to gravid Sprague-Dawley rats by oral gavage on gestational days (GD) 6-20. The low dosage contained ST extract equivalent to 1.33 mg/kg nicotine (STD-1), and the high dosage contained ST extract equivalent to 4.0 mg/kg nicotine (STD-2). Dams were dosed three times daily at 8 a.m., 11 a.m., and 2 p.m., thus providing total daily nicotine equivalent dosages of 4 mg/kg/day and 12 mg/kg/day. Controls received equivalent amounts of distilled water by gavage. Dams were allowed to deliver and all experimental pups were fostered to control mothers. 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-weaning periods. Behavioral tests included: surface righting, negative geotaxis, swimming development, open-field activity, active avoidance in shuttle box, and Cincinnati swimming maze. Our results show that the STD-2 dose resulted in reduced maternal weight gain. Offspring weights were reduced in a dose-related manner, with the most consistent weight deficits seen in the STD-2 group until PND29. Consistent STD-1 weight deficits were seen up to PND 8. The incidence of deaths was increased in the STD-2 dosage group. No significant treatment-related differences were observed in development of physical landmarks. Male STD-2 pups righted faster than controls, and significant differences were noted in swimming development with the STD-1 group of pups performing less effectively than controls. Activity levels, assessed during both pre- and post-weaning periods were not affected. No treatment-related differences were seen in the active avoidance shuttle box or Cincinnati swimming maze tests, which assessed learning. Female brain weights were reduced in the STD-1 treatment group.
Paulson
R B
RB
Department of Oral Biology, College of Dentistry, Ohio State University, Columbus 43210-1241.
Shanfeld
J
J
Vorhees
C V
CV
Sweazy
A
A
Gagni
S
S
Smith
A R
AR
Paulson
J O
JO
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D005260:Female; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009538:Nicotine / Q000633:toxicity; D009929:Organ Size / Q000187:drug effects; D010947:Plants, Toxic; D004856:Postural Balance / Q000187:drug effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013550:Swimming; D014030:Tobacco, Smokeless / Q000633:toxicity*
D009538:Nicotine