ABSTRACT
To confirm genetic variation in low-dose effects of diethylstilbestrol (DES), two inbred strains of rats, which have been selectively bred for high- and low-avoidance learning (HAA and LAA, respectively), were used in this study. LAA rats characteristically show later sexual maturation, earlier reproductive senescence, and lower body weight as compared to HAA rats. Female neonates of each strain were daily administered DES by oral gavage at doses of 0 (vehicle only), 0.05 and 0.5µg/kg for the first 5days after birth. As a result, early onset of abnormal estrous cycles was observed during the same period in HAA and LAA rats treated with 0.5µg/kg. However, accelerated puberty and excessive body weight gains were observed only in LAA rats treated with 0.05 and 0.5µg/kg. These results suggest that the effects of neonatal DES exposure vary with the genetic background of the female rats used.
Subject(s)
Carcinogens/toxicity , Diethylstilbestrol/toxicity , Estrogens, Non-Steroidal/toxicity , Animals , Animals, Newborn , Avoidance Learning/drug effects , Body Weight/drug effects , Estrous Cycle/drug effects , Female , Genetic Variation , Pregnancy , Rats , Rats, Inbred Strains , Sexual Maturation/drug effectsABSTRACT
In the present study, in order to reveal novel adverse effects of ultrafine particles (UFP) on the central nervous system, the effects of nanoparticle-rich diesel exhaust particles (NRDEP; count mode diameter, 21.45 nm) on emotional behavior, learning capability and brain neurotransmitter levels were studied in rats by intranasal instillation (iNI). NRDEP (10 and 50 µg/rat) was instilled into 2-week old infant, male rats once a week for 4 weeks. Spontaneous motor activity measured was observed to be inverse to the dose level. In active avoidance tests using a shuttle box, NRDEP-treated animals showed a lower avoidance performance than control animals given air-instillation. The levels of dopamine and its metabolite (DOPAC) in the medial mammillary nucleus of the brain tended to be lower in the NRDEP-treated animals. From these results, although the effects of NRDEP by iNI on the emotionality and the brain neurotransmitter levels were not fully clear, the results obtained by avoidance testing suggested involvement of UFP in learning capability.
