Bradley A. Lown

Effects of in utero or suckling exposure to cerium (citrate) on the postnatal development of the mouse.

Gravid female mice received either a single subcutaneous dose of cerium citrate (80 mg Ce/kg) or an equivalent (in citrate) dose of sodium citrate on d 7 or 12 of gestation or on d 2 postpartum. To separate effects of prenatal and postnatal exposure, a cross-fostering design was employed. The weight and gross activity of the neonates were assessed on d 8 or 13 postpartum. Open-field behavioral parameters, accelerating rotarod performance, and passive avoidance learning were assessed on d 60-65 postpartum. Maternal offspring retrieval latency was measured on d 3 postpartum. Analyses revealed that neonatal weight was reduced both in offspring exposed to Ce in utero and in the offspring of mothers receiving Ce during lactation/suckling. Ce also appeared to affect maternal/offspring interaction: pups exposed prenatally to Ce were retrieved in less time than control pups. Except for an increased frequency of rearings in the open field of adult offspring exposed to Ce in utero, Ce exposure had no apparent effect on behavioral parameters, either in neonatal or adult offspring.

Differential effects of acute methylmercury poisoning in the mouse arising from route of administration: LD50, tissue distribution and behavior.

1. 1. Methylmercuric chloride (MeHg: 10 mgHg/kg body wt containing 1–2 μCi Me203HgCl) in phosphate buffered saline (PBS; pH 7.4) or PBS alone were administered to male mice (10/group) intragastrically, intramuscularly, intraperitoneally, intravenously or subcutaneously. 2. 2. Open-field behavior (ambulations, rearings) was monitored at 10 min, 3 hr, or 3 days post administration. 3. 3. Anova revealed significantly (P < 0.05) depressed ambulations and rearings (MeHg vs PBS) mainly due to the intraperitoneal route. 4. 4. Significant differences in tissue concentrations were found across time and route. 5. 5. However, regression analysis revealed modest associations only between liver and kidney levels and behavioral measures and no associations between brain levels and behavior. 6. 6. Thus, behavioral alterations were not directly related to brain Hg levels.

Effects on open-field behavior of mice exposed to multiple doses of methyl mercury.

Abstract 1. 1. Effects on open-field behavior (rearings and ambulations) of mice given multiple doses of methyl mercury (MeHg) were investigated. 2. 2. Groups of Swiss-Webster mice received 1–10 intraperitoneal (i.p.) doses (2·5 mg Hg/kg body wt) of MeHg in 0·14 M NaCl (controls received vehicle only). Doses were administered at 72 hr intervals. Behavioral parameters were monitored 72 hr post administration. 3. 3. Rearings significantly decreased as a function both of toxicant (MeHg vs saline) and total dose. This effect was localized, occurring after the 6th dose when brain uptake of Hg had plateaued. 4. 4. Concentration of Hg in the cortex and cerebellum correlated significantly with the decreased rearings.

Effects on the development of offspring of female mice exposed to platinum sulfate or sodium hexachloroplatinate during pregnancy or lactation

On d 7 or 12 of gestation or on d 2 postpartum, Swiss ICR dams were administered either (1) a single intragastric dose of Pt(SO4) at the LD1 level or dilute H2SO4 at an equivalent volume, pH, and sulfate content, or (2) a single subcutaneous dose of Na2PtCl6 or phosphate-buffered saline at an equivalent volume and pH. To differentiate prenatal from postnatal effects of the compounds on the offspring, a full cross-fostering design was employed. Rate of growth (as a function of weight gain) and gross activity of the neonates were assessed on d 8 or 13 postpartum. On d 60-65 postpartum, open-field behavior (ambulations and rearings), rotarod performance, and passive avoidance learning of the adult offspring were investigated. Exposure to Pt(SO4)2 resulted in reduced offspring weight from d 8 to 45 postpartum, whereas the major effect of Na2PtCl6 was a reduction in activity level of the offspring of mothers exposed on d 12 of gestation.

Time-dependent tissue/organ uptake and distribution of 203Hg in mice exposed to multiple sublethal doses of methyl mercury.

Abstract Swiss-Webster mice were injected intraperitoneally with one to ten doses (2.5 mg Hg/kg) of 203Hg-labeled methyl mercury. Doses were administered at 72-hr intervals. Maximal tissue/organ Hg uptake usually occurred 72 hr postinjection and was monitored at 3 and 6 days by gamma scintillation spectrometry. Most tissues/organs required five to six doses to attain maximal Hg concentrations (the carcass required seven doses; hair and fat, eight doses; lens, nine doses). Data for hair were highly variable. Except for hair (which required seven to eight doses), maximal tissue/organ concentration factors (CF) were reached 72 hr after the first dose. Kidney, liver, and hair attained CF values > 1. Except for hair, all CF values decreased with increasing dose number. Initial rates of decrease were much greater for kidney, blood, spleen, muscle, and liver than lens, brain, and fat. Only hair exhibited a significantly higher Hg concentration at 6 days after each dose than at 3 days. With increasing dose number, blood Hg; tissue/organ Hg ratios remained relatively constant for liver, kidney, spleen, and muscle; decreased for lens and brain; and decreased for hair and fat after an initial increase.

Cerium tissue/organ distribution and alterations in open field and exploratory behavior following repeated exposure of the mouse to citrate complexed cerium

1. 1. The tissue distribution and effects of Ce on open-field and exploratory behavior was investigated in 6–8 week old random bred male Swiss mice (ICR strain). 2. 2. The experimental subjects received 1–10 doses (s.c. at 3 day intervals) of 20 mg Ce/kg body weight (equivalent to 0.1 × 7 day LD50 dose). Ce was administered in the form of a 1:3 CeCl3:sodium citrate complex (adjusted to pH 7.4 with NaOH), containing 0.3 μ Ci 141Ce, in a volume equivalent to 1.0% (v/w) body weight. Similarly, control animals received 105.3 mg sodium citrate/kg. 3. 3. Three days post administration of the final dose of each series, the open-field (ambulations and rearings) and exploratory (“hole-in-board”) performance of 10 randomly selected experimental and control animals were quantified. Half the animals were observed first in the open-field and then in the exploratory apparatus and vice versa. 4. 4. Tissue Ce levels were determined by γ scintillation spectrometry. 5. 5. Overall, compared with controls, Ce exposed animals exhibited significantly (P < 0.05) depressed ambulations and marginally (P < 0.08) depressed explorations. 6. 6. Spleen, liver, bone and lung contained the highest Ce concentrations and no decrease in tissue Ce concentrations was observed up to 98 days post exposure. 7. 7. No correlation between behavior and tissue Ce levels was observed.

Alterations in active avoidance acquisition in the guinea pig following septal lesions at three ages

The behavior of guinea pigs in a two-way active avoidance apparatus was examined after lesions of the septal area at three different age levels. The effects of the septal lesions were identical at all ages. In all age groups, septal lesions caused a facilitation of the avoidance behavior. The failure to find age differences was interpreted in terms of the relatively advanced brain development of precocial animals at birth.

Effects of Early Handling on Open-Field Activity of Gerbils

An experimental group of nine neonatal gerbils was handled from Day 1 to Day 21 post partum while a control group was not handled. At 60 days of age both groups were tested in an automated open field. The handled group had significantly fewer ambulations than the non-handled group. This is opposite to the handling data from rats and mice.

Effects of acute exposure to cerium (citrate) on selected measures of activity, learning and social behavior of the mouse

Abstract 1. 1. The effects of cerium (citrate) on long-term general activity (activity wheel behavior), passive and active avoidance learning and a measure of social behavior were investigated in random-bred male Swiss mice. 2. 2. Cerium (Ce) was administered subcutaneously at the LD 5 or LD 25 level in a volume equivalent to 1.0% (v/w) of body weight. 3. 3. in the passive avoidance study, additional groups of subjects received a single intragastric (i.g.) dose of Ce at the i.g. LD 5 or LD 25 . 4. 4. Control animals received equivalent volumes of sodium citrate at a concentration equivalent to that of the LD 25 dose. Individual subjects were tested only on one behavioral task. 5. 5. Statistical analysis revealed a significant depression of activity wheel running from 4 hr through 7 days (termination of experiment) post Ce administration. 6. 6. Cerium had no significant effect either on passive or active avoidance learning. However, Ce depressed the activity components of both of these tasks. 7. 7. Cerium had no significant effect on the measure of social behavior investigated; but, as in the other behavioral tasks, the activity level of the Ce-dose animals was depressed.

Effects of food deprivation on open-field behavior of mice exposed to methyl mercury.

The joint effects of methyl mercury and food deprivation on activity of 40 mice in an open field were examined. Analysis gave a significant main effect for mercury but not deprivation, and a significant interaction between mercury and deprivation. Simple tests indicated that food deprivation enhanced the depression of activity associated with exposure to mercury.