Donald E. Clark

Dietary lead increases ethanol consumption in the rat

Rats fed either a diet containing 500 ppm (parts per million) Pb (as lead acetate) or an unadulterated control diet for 50 days were offered a 15% ethanol (ETOH) solution in a nonchoice (one-bottle) test situation. The results from this test indicated that Pb-diet animals consumed greater amounts of the ETOH solution than did controls. In a subsequent choice (three-bottle, two-fluid) test situation offering a nonpreferred ETOH solution or tap water as alternatives, Pb-diet animals once again ingested greater amounts of the ETOH solution. These findings are discussed in terms of possible Pb-induced increases in emotionality and the potential stress-reduction properties of ETOH.

Effects of dietary cobalt on testicular structure.

SummaryAdult male rats were maintained on a diet containing 265 ppm cobalt for up to 98 days. Three rats were sacrificed weekly and assayed for testicular damage by light and electron microscopy. Testicular damage was first apparent after 70 days of treatment, followed by a progressive deterioration of cell architecture and decrease in testicular volume. The degenerative changes were of a very general nature; e.g., thickening of basal lamina and basement membranes, increased packing of red blood cells in veins and arteries, formation of “giant” cells, loss of sperm tail filaments, and degeneration of sperm mitochondria. No cobalt residues could be detected by energy dispersive x-ray microanalysis. These data indicate that testicular degeneration was not a primary response to cobalt and suggest that the testes become hypoxic due both to blockage of veins and arteries by red blood cells and to changes in permeability caused by thickening of basal lamina and basement membranes.

The effects of oral cadmium exposure on passive avoidance performance in the adult rat

Step-down passive avoidance acquisition and 24 h retention performance were examined in adult rats given daily doses of either 0, 1, or 5 mg/kg cadmium (Cd) (as CdCl2) via the diet. Results indicated that subjects exposed to the 5 mg/kg Cd diet were less likely to step off a safe platform onto an electrified grid floor than controls. The 1 mg/kg subjects did not differ from controls on this acquisition task. None of the groups showed differential performances on a retention test administered 24 h after acquisition training. These results are discussed in terms of recent claims that Cd exposure enhances emotional reactivity in animals.

The effects of cadmium on the self-administration of ethanol and an isocaloric/isohedonic equivalent

During a period of baseline fluid intake recording, adult male rats were presented with a three-bottle, two-fluid choice test that offered either a 10% ethanol solution (v/v) and tap water as alternatives, or a sucrose/quinine solution and tap water as alternatives. The sucrose/quinine solution was equivalent to the ethanol solution both in terms of calories and palatability. After intakes stabilized, half of the animals from each test condition were placed on a diet containing 100 ppm cadmium and the remaining half of the animals were placed on a standard laboratory diet. After 60 days of exposure to their respective diets, all animals were presented their earlier test solutions, both in a nonchoice and choice format. The results from the choice test indicated that although cadmium treatment did not produce a clear preference for ethanol over water, cadmium exposure was associated with a significant increase in ethanol consumption. Moreover, the self-administration of the isocaloric/isohedonic equivalent (sucrose/quinine solution) was unaffected by cadmium contamination. These data are discussed in terms of their implications for both nutritional and sensory-impairment accounts of metal-related changes in the volitional intake of ethanol.

Effects of vomitoxin (deoxynivalenol) on conditioned saccharin aversion and food consumption in adult rats

Vomitoxin is a trichothecene mycotoxin that induces feed refusal. Experiment I evaluated the potential aversive action of vomitoxin in a conditioned taste aversion paradigm. Adult male rats were fed either a control chow diet or a diet adulterated with 640 ppm lithium chloride (positive control) or with 2, 4 or 8 ppm vomitoxin and given access to a 0.1% saccharin solution and tap water during three training days. The rats were then shifted to a plain chow diet during 5 extinction days. Vomitoxin (8 ppm) and the positive control diet induced marked taste aversion commencing on the first day of exposure. Rats fed the 4 and 8 ppm vomitoxin diets ate less food only on the first day of contaminated diet exposure. Experiment II evaluated the potential action of vomitoxin on food palatability. Adult male rats were fed a powdered commercial chow for 5 days and then offered, in a preference test, a choice of chow and either: the same chow or chow adulterated with either 0.25, 0.50, 1.0, 2.0, 4.0 or 8.0 ppm vomitoxin. Relative to the total food intakes and the choice ratios (control chow consumed/total chow consumed) of the chow-chow groups, adulteration with 8 ppm vomitoxin resulted in a significant reduction in overall food intake, but not in food choice ratio and this effect of vomitoxin on feed consumption was observed only on day 1 of exposure. Vomitoxin, at 4 and 8 ppm, does not alter food palatability but does induce conditioned saccharin aversion.

Cadmium exposure results in decreased responsiveness to ethanol

Adult male Sprague-Dawley rats were maintained on an ad lib diet containing 100 ppm cadmium (Group Cadmium-Diet) or a control diet with no added cadmium. On Day 61, all animals (N = 10/group) were challenged with a single hypnotic dose of ethanol (3.5 g/kg IP), prepared from a 20% v/v solution of tap water and a stock solution of 95% ethanol. The latency from the time of the injection until the loss of the righting reflex was recorded, as well as the latency for recovery of the reflex. The results showed a nonsignificant trend for animals exposed to cadmium to lose the righting reflex less rapidly than controls, and Cadmium-Diet animals regained the righting reflex significantly more rapidly than controls. These findings suggest that the pharmacologic effectiveness of ethanol is altered by chronic exposure to dietary cadmium. The implications of these data for other studies of cadmium/ethanol interactions are discussed.

Dietary administration of nickel: Effects on behavior and metallothionein levels ☆

Adult male rats were fed either 0, 10, or 20 mg Ni/kg body weight (as NiCl2) via a 10 g daily food ration. Following 14 days of exposure, animals were trained over a period of 61 days to lever press for food on a VI-2 operant training schedule while continuing to experience the indicated daily doses. Those rats treated with 20 mg/kg Ni lever pressed at a significantly lower rate than controls. Group 10 mg/kg subjects were not significantly different on this behavioral measure than control subjects. Atomic absorption spectrophotometric analysis revealed a dose/response accumulation of Ni in the kidney, but analyses of blood, bone, brain, hair, small intestine, liver, and testes did not show differential agent accumulations. Neither hepatic nor renal metallothionein levels were increased above control levels. These findings were discussed within the framework of other recent behavioral and biochemical studies of heavy metal toxicity.

Behavioral effects of chronic lead exposure in the adult rat

Adult rats fed daily rations of laboratory chow laced with lead acetate, were tested for operant (schedule-controlled) responding and conditioned suppression. In Experiment 1, animals receiving 10 mg/kg lead showed significantly lower operant response rates (lever pressing) than controls. Conditioned suppression performance was not different between the two groups. During retraining that followed a 42 day no-training period, lead-treated subjects showed greater percent of prior baseline responding than controls. The groups were not different on a test for stimulus control or an appetitive resistance to extinction test. In Experiment 2, separate lead-treated groups were chronically exposed to either 10 mg/kg, 5 mg/kg, or 1 mg/kg lead daily. Behavioral tests showed that while the lowest lead level (1 mg/kg) occasioned higher rates of operant lever pressing relative to controls, the highest level (10 mg/kg) again produced lower rates. On a retraining task administered after an interpolated 90 day no-training period, the two highest exposure groups were significantly above controls regarding percent of baseline responding and there was evidence that the 5 mg/kg group was significantly superior to controls in terms of absolute response rate. No differences in conditioned suppression or resistance to extinction were observed in the second experiment.

Effects of T-2 toxin on saccharin aversion and food consumption in adult rats

The present experiment used a saccharin aversion paradigm to evaluate the potential aversive action of T-2 toxin, a trichothecene mycotoxin that induces emesis and weight loss. Adult male rats were fed either a control diet or a diet adulterated with 640 ppm lithium chloride (positive control) or with 2.5, 5.0 or 10.0 ppm T-2 toxin and given access to a 0.1% saccharin solution and to tap water during four training days. The rats were then shifted to the control diet during three extinction days. Moderate saccharin aversion induced by the positive control diet and the 5.0 and 10.0 ppm T-2 diets was apparent on the third day of exposure and the aversion to the saccharin solution abated during the extinction trials. Saccharin aversion was evident at levels of T-2 toxin that did not induce obvious tissue pathology.

Conditioned suppression in the adult rat following chronic exposure to lead

Conditioned suppression was examined for control (N = 8) and lead-treated (N = 8) adult rats. Treated animals were exposed daily to 10 mg/kg lead administered via the diet as lead acetate. 40 days of operant lever press training on a multiple schedule using food as reward was given. Lever press training continued for an additional 5 days but during this period subjects experienced superimposed 3 min tone presentations followed by electric shock (1.3 mA, 1.5 s duration) to a grid floor. Tone presentations were observed to be significantly more disruptive of operant steady state responding for treated subjects as compared to controls. This finding supports earlier claims that lead exposure enhances emotionality.