Effects of time of day on chlorpyrifos-induced alterations in body temperature.

Chlorpyrifos (CPF) is an organophosphate (OP) insecticide and is among the most common and widely used commercial insecticides. Human intoxication is reported to result in a typical set of responses, which include an immediate and long lasting hyperthermic response (fever). Rodents exposed to similar doses exhibit a biphasic body temperature response: short-term hypothermia followed by subtle hyperthermia several days after administration. Time of day of administration has been suggested to alter the body temperature effect of CPF. In the present study, it is shown that adult male Sprague-Dawley rats exposed to CPF via (oral) gavage at four different times of the day demonstrate a hypothermic response, the timing and magnitude of which is independent of time of exposure and that is blocked by atropine pretreatment. However, a delayed (hyperthermic) response seems to be exhibited only when dosing occurs during the light phase. Our findings support existing theories that the hypothermic and hyperthermic effects of CPF work through independent mechanisms. It is also suggested that humans may indeed exhibit a biphasic temperature response to CPF intoxication, but that it is not typically detected.

Behavioral responses to repeated cocaine exposure in mice selectively bred for differential sensitivity to pentobarbital.

Mice from the 20th generation of three lines divergently selected for response to pentobarbital-induced sedation times [long-sedation time (LST), short sedation time (SST), and randomly bred control (RBC)] were used to study cocaine-induced behavioral sensitization. These lines showed variable degrees of locomotor activities in response to cocaine. At a low cocaine dose and long withdrawal period (10 mg/kg, twice a day for 5 days followed by a 14-day withdrawal), the LST mice showed tolerance development. In response to cocaine, the locomotor activities of the SST were not significantly different from the RBC group. At a higher dose and a shorter withdrawal period (20 mg/kg, daily for 7 days followed by a 3-day withdrawal), the SST mice showed behavioral sensitization similar to the RBC mice, but the LST mice did not develop sensitization. The different responses in locomotor activity induced by cocaine suggest that genetic factors may play a role in determining the magnitude of response to this drug. Dopamine (DA) levels did not differ significantly in either striatum (STR) or nucleus accumbens (NAC) for the cocaine-treated animals to their corresponding saline-treated controls. The affinity (Kd) of D2 in the NAC decreased significantly, without changes in density (Bmax), in the cocaine-treated SST and RBC mice. On the other hand, the density of D2 binding sites in the SST and the RBC mice in the STR was significantly increased in cocaine-treated groups without change in Kd. The LST mice did not show any changes in the Kd and Bmax in either the STR or the NAC. Taken together, these findings suggest that the changes in the Kd of D2 in the NAC and the Bmax of D2 in the STR may contribute to the differences in locomotor responses to cocaine exposure in these mouse lines.

The effect on performance and biochemical parameters when soil was added to aflatoxin-contaminated poultry rations.

The effects of silty clay loam soil on the performance and biochemical parameters of chicks were investigated when the soil was added to aflatoxin B1 (AFB1)-contaminated diets. One hundred 14-d-old White Leghorn chicks were fed a control ration (clean corn), a low aflatoxin-contaminated ration (120 ng AFB1/g), a high aflatoxin-contaminated ration (700 ng AFB1/g), or high aflatoxin-contaminated rations (700 ng AFB1/g) +10% or 25% soil. Body weight, feed consumption and blood samples were monitored weekly. Decreased feed consumption, body weight gain and efficiency of feed utilization, increased SGOT and LDH activities, and cholesterol and triglyceride concentrations, and decreased uric acid concentrations and ALP activity were observed in the chicks fed the high aflatoxin-contaminated ration without soil. Hepatomegaly was prominent in chicks fed the high aflatoxin-contaminated ration without soil, and some livers had extensive hepatocyte vacuolation, hepatocellular swelling, fatty change and hydropic degeneration, and stained positive for fat accumulation. Addition of soil reduced the detrimental effects of AFB1 for some parameters, although the reduction was less when 10% soil was fed compared with the 25% soil feeding.

The genotoxicity and cytotoxicity of dermally-administered cadmium: effects of dermal cadmium administration.

Cadmium, unlike zinc, selenium and copper, has no known biological importance, and therefore, it is classified as a carcinogen in humans, as well as in animals. The effect(s) of levels of dermally-administered cadmium on cadmium genotoxicity and cytotoxicity was investigated in Harlan Sprague-Dawley rats for 14, 21, 28, 35 and 42 days at concentrations of 14 and 28 mg/kg/day. Exposure of rats to cadmium via dermal application caused lesions on the skin (hyperkeratosis, acanthosis and scabbing, alopecia and erythema) and tumors in the scrotum. Anatomical changes, such as distention of the stomach, atrophy of kidney and liver and loss of body weight were also observed in these rats. The toxic effects of cadmium on cell ultrastructure were nuclear membrane damage, chromatin condensation, regression of mitochondrial cristae and ultimately cell death. Analyses of the brain, kidney and liver cells of rats exposed to cadmium, clearly showed DNA damage. Of the three organs examined, DNA from kidney cells sustained the most damage followed by DNA in liver cells. There is a positive correlation between Cd dose(s) and duration of exposure and the extent of DNA damage.

Divergent selection for pentobarbital-induced sedation times in mice.

Divergent selection for pentobarbital sedation-time response was practiced in mice for 9 generations. At the end of 9 generations of selection, the long-sedation-time line (LST) slept an average of 433 min; the short sedation time line (SST) slept an average of 29 min. The control line (C) slept an average of 71 min. These differences represent an almost 15-fold increase in sedation time for the LST compared to the SST line and a 6-fold increase compared to the C line. The SST line slept about 40% less than the C line after 9 generations of selection (measured in tenth generation progeny). Analysis of selection differentials and realized heritabilities indicated that selection response did not diminish after 9 generations of selection. Realized heritabilities for sedation time ranged from 0.43 to 0.83 for the LST line and from 0.55 to 0.81 for the SST line. Realized heritabilities did not decrease in magnitude due to selection progress, indicating that more progress can still be achieved. Comparing corrected (for environmental factors) to uncorrected heritabilities showed the importance of including a control line in selection experiments. Crossing of lines to study gene action responsible for this trait revealed that this trait was controlled by a number of genes with additive gene action without dominance, overdominance, epistasis, or maternal effects.

Hypothermic effect of ethanol in mice selected for differential sleep-time response to pentobarbital.

The hypothermic action of ethanol was investigated in genetically distinct lines of mice selected for sleep-time response to pentobarbital for six generations. Ethanol (3 g/kg, intraperitoneally) was administered to alcohol-naive males and females from each of the unselected control, long-, and short-sleep mouse lines. Rectal temperatures were measured immediately before, and at 15, 30, 60, 90, 120, and 240 min after ethanol injection. Eight female and eight male mice from each line were sacrificed at each time point, and trunk blood was collected for plasma ethanol analysis. The results show that short-sleep mice were less hypothermic (p < 0.05) compared to long-sleep mice at 15 and 30 min after ethanol administration. However, plasma ethanol concentrations were not significantly different between the mouse lines at any time point. Therefore, the line-dependent differential ethanol-induced hypothermia observed may be a result of differences in "brain sensitivity" rather than in the rates of ethanol metabolism among the mouse lines.

Single gene effect on alcohol preference in the Zucker rats.

Zucker obese (ZO), Zucker lean (ZL), and Sprague-Dawley (SD) naive rats of both sexes were used to study the role of the fa/fa gene on alcohol preference. During the first two weeks of this experiment (weeks 1-2) all rats received a 10% alcohol solution ad lib as the only source of liquid. Animals were then given free access to both water and alcohol for the following three weeks (weeks 3-5). Thereafter, rats were deprived of alcohol every other day for two weeks (weeks 6-7), then completely deprived of alcohol for one week (week 8). Finally, unlimited access to both water and alcohol solution was available for the last two weeks of the experiment (weeks 9-10). Results of this study show that when rats were offered both water and alcohol (weeks 3-5), ZL rats consumed significantly more alcohol (2.5-fold) than their littermates, the ZO rats and the SD rats. Similarly, during alternate days of alcohol deprivation (weeks 6-7), ZL rats consumed significantly more alcohol (threefold) than the ZO rats and the SD rats. After a week of alcohol deprivation (week 8), and during the final two weeks (weeks 9 and 10), ZL rats continued to consume significantly more alcohol (2.5-fold) than the ZO group or the SD group. ZL females consumed more alcohol per kg body weight than male ZL rats. Data obtained from this study suggest that in the Zucker rat a single gene can alter the animal alcohol preference.

Divergent selection for pentobarbital-induced sleeping times in mice.

A pharmacogenetic model for sensitivity of mice to pentobarbital is being developed by selection for sleep-time response. One generation of divergent selection for long and short sleep-time in mice resulted in a 19% increase in the long-sleep line and a 15% decrease in the short-sleep line. Calculated heritability estimates averaged 0.49 and realized heritabilities averaged 0.24. The extent of the selection progress and the heritability values indicate that genetic constitution plays a major role in controlling variations of sleep-time response to pentobarbital.

Effects of monensin-feeding regimens on flock immunity to coccidiosis.

Feed medication with monensin caused delays in development of immunity in two floor-pen experiments which simulated commercial broiler production. Development of immunity was retarded with the higher level of monensin (120 p.p.m.) but was progressively less delayed as the monensin level was decreased (100, 60 or 0 p.p.m.). Delay was greatest with Eimeria tenella, but also occured with intestinal species including E. acervulina, E. brunetti, E. maxima, E. mivati, and E. necatrix. Drug withdrawal permitted earlier development of immunity. Plans involving use of monensin on layer replacements which later will be maintained on the floor without medication should consider: 1) prevalence of infective oocyst exposure in the area, 2) the lowest possible level of drug required for protection, and 3) its use for the shortest possible period of time.

Divergent Selection under Two Nutritional Environments for Packed Erythrocyte Volume in Japanese Quail.

Two-way selection for two-week packed erythrocyte volume (PCV) was practiced for four generations under two nutritional environments in the Japanese quail (Coturnix coturnix japonica). One environment was an iron, copper-"adequate" diet and the other was iron, copper-deficient "stress" diet. Response to selection was greater in both directions under the adequate environment than under the stress environment. After four generations of selection there were 29% and 18% differences between the high and low lines under the adequate and the stress environments, respectively. An asymmetry of response was observed toward the low line under the adequate environment and toward the high line under the stress environment. The realized heritability estimates for the high and low Fe-Cu-adequate lines were.26 and.35, respectively, while those for the high and low Fe-Cu-deficient lines were.16 and.06, respectively.