Neurobehavioral toxicology最新文献

The purpose of the present study was to design a standard battery of tests capable of quantitatively characterizing ataxia and concomitant neurological signs in the rat. In addition to a systematic analysis of the walking gait of animals, tests for activity, catalepsy, rigidity and various reflexive responses were included in the battery. The standardization of the test system was performed by determining and comparing neurobehavioral effects produced by 3-acetyl pyridine, acrylamide, pyrithiamine and thiamine deficiency, four experimental treatments reported to induce ataxia in animals. Results indicate that profiles of neurobehavioral disturbances accompanying ataxia in animals varied distinctively with each experimental treatment.

Broad agreement on specific approaches or standardized test batteries for assessing behavioral toxicity is unlikely to emerge in the foreseeable future. EPA should reject test standardization in any case, however; standardization stifles progress and, in addition, may bypass unique properties of new types of substances. The optimal strategy is to prescribe a set of functions, such as sensory, motor, and complex performance processes, leaving it to the manufacturer to select adequate tasks. Adequacy would be judged by EPA staff, in consultation with advisory panels, and resolved, in most cases, by a dialogue with the manufacturer.

Two sets of observations are reported as illustrations of problems encountered in behavioral toxicology. First, in an attempt to determine the contribution of methylmercury-induced ataxia to behavioral changes observed on the fixed-consecutive-number schedule, some ancillary control experiments were undertaken. Neither pharmacologically-produced incoordination (ethanol) nor mechanically-produced incoordination (foot taping) led to behavioral changes similar to those seen after exposure to methylmercury. Second, total crop impaction in a pigeon that died during a behavioral experiment on lead suggested some further work. Lead-induced crop stasis in pigeons was measured by x-raying the passage of force-fed stainless steel ball bearings through the crop. This retardation of motility reliably preceded signs of overt toxicity. These results suggest that the behavioral changes in the pigeon noted by us and reported by other investigators cannot be attributed to CNS dysfunction alone, but more likely arise from starvation, or from combined CNS damage and starvation. In addition, these results demonstrate that the appearance of behavioral effects prior to overt toxicity does not necessarily reflect CNS damage.

A technique has been developed that allows infant monkeys to perform on an operant schedule as soon as they are able to self-feed. Behavior is shaped in small increments through a series of operants; sensory and motor systems as well as performance on schedules using intermittent reinforcement may be tested as early as 3-4 weeks of age. This is accomplished by exposing the infant to the operant situation almost continuously, and allowing the infant to feed only by operantly responding. Infants exposed to lead post-natally differed from controls in pattern of fixed ratio responding, "activity" as measured by pattern of responding over the course of the session, and on a two-choice form discrimination reversal learning set paradigm. This technique allows rapid accumulation of large amounts of data without experimenter intervention.

Rats received 3H-mannitol, which marks the intactness of the blood-brain barrier, and 14C-glutamate or 14C-aspartate by intracardiac injection after oral gavage with water, monosodium glutamate, monosodium aspartate, or sodium chloride (doses equiosmolar to 4 g/kg monosodium glutamate). Thirty min later, various brain regions (e.g., cerebellum, cortex, hypothalamus, and striatum) were assayed for tritium and carbon-14. In most regions in most animals given monosodium glutamate or hypertonic saline, the level of the carbon-14 acidic amino acid tended to parallel the extent of damage incurred by the blood-brain barrier, as indicated by high levels of tritium-labelled mannitol. These data suggest that severe hyperosmolarity may be a prerequisite for monosodium glutamate to produce neurotoxic changes, and may explain why elective dietary consumption of enormous quantities of glutamate, by animals given free access to water, fails to induce brain lesions.

Rats exposed to lead via the maternal milk were tested at maturity on three different visual discrimination tasks. Starting at parturition the dams were given either tap water, 0.20% sodium acetate, 0.02% lead acetate, or 0.20% lead acetate in the drinking water. At weaning, the pups from all the groups were placed on normal chow and tap water. At 20 days of age, the concentration of lead in the blood and brain of the high lead-exposed offspring was approximately 6 times that of controls (11 microgram% vs 66 microgram%). A significant deficit was found in the ability of the high lead-exposed group to acquire a simultaneous visual discrimination task conducted in an operant chamber. No significant differences were observed in the ability of lead-exposed rats to acquire either a successive visual discrimination task or a cued go/no-go discrimination. Thee results suggest that early lead exposure can affect certain behavioral processes and that the effects may persist even after the rat has reached maturity.

A technique to measure the fore-and hindlimb grip strength of rats (adult and preweanling) and mice is described. the procedure utilizes inexpensive equipment, is rapid and efficient, and provides continuous level data. As a means of validating the sensitivity of the test, the effects of phenobarbital and chlordiazepoxide on the grip strength of adult Fisher strain and Sprague-Dawley derived adult rats were investigated. Dose-related decreases in fore- and hindlimb grip scores were observed in both strain of rats. The interanimal variability in this test was less in Fisher rats than in Sprague-Dawleys. The technique appears to have a great deal of potential in studies concerning the neuromotor effects of environmental and psychopharmacological agents.

In two experiments, Sprague-Dawley rats were administered elemental selenium (Se; 10 ppm), silver (Ag; 1000 ppm) and arsenic (As; 50 ppm), either alone or in combination (Ag+Se or As+Se). Administration was via drinking water. Body weight, fluid intake, and food consumption were monitored weekly and measures of forelimb and handlimb strength were taken. Se depressed body weights in both experiments, as did As+Se. Food consumption relative to body weight tended to be increased by Se alone; none of the other treatments affected body weight, except for As+Se. Water consumption was depressed in all cases, which was attributed to a palatability effect. Limb strength was not affected by any treatment. The addition of Ag to the drinking water containing Se appeared to reduce the toxic effect of Se. However, As appeared to interact in a potentiating fashion with Se. There was 1 death in the Se alone group, none in the As group, but 7 out of 10 animals receiving As+Se had died by the end of the 18 week dosing period.