Neurobehavioral toxicology最新文献

Behavioral conditioning together with conventional sensory testing methods may be used in the evaluation of toxic effects on sensory systems in experimental animal models. Such procedures yield precise quantitative estimates of impairment in absolute and differential acuity and in sensory perception. Additionally, these behavioral changes can be related to the presence of histopathology in peripheral sensory structures; this orderly relation between structure and function may aid in our understanding of the basis for sensory coding in the normal end organ.

Operant conditioning techniques have been shown to be sensitive to the acute effects of industrial solvents. In the first experiment, five rats trained in a multiple schedule with a fixed-ratio (FR) 10 component and a differential reinforcement of low rates (DRL) 20-sec component, with a time out 60-sec between reinforcement periods, were exposed to 0.25, 0.50, 1 and 2 ml of toluene in the experimental chamber. The effects were dose-dependent, with an increase in rate in the DRL component and a decrease in FR responding. A second experiment assessing the effects of chronic exposure to thinner in the acquisition of a timing behavior in rats showed an impairment in DRL learning after 4, 8 or 16 weeks of exposure to the solvent: however, rats having a resting period did not differ from control animals. Whereas this finding suggests a reversible impairment in the acquisition of a complex behavior, further research is needed to achieve more definitive conclusions.

Literature relevant to the relationship between early ingestion of inorganic lead and subsequent hyperactivity in rodents is discussed. Original research in the area is presented. Rats so exposed were not hyperactive in any of the situations investigated or under any of the dosage regimens employed. They did show hypoactivity in the open field when dosed over a prolonged period. Using a new behavior measure, lead-treated rats were found to be less active than controls in the passive avoidance situation. The possible utility of this new measure for behavioral and developmental toxicology is discussed. It is concluded that the available evidence does not support the contention that a meaningful relationship exists between early lead ingestion and hyperactive behavior. It is suggested that future research may more profitably be directed to assessing the effects of lead ingestion on behavior in stressful or fear provoking situations.

Laboratory procedures have been developed for the experimental analysis of risk-taking and psychophysical functions in dog-faced baboons (Papio anubis). In a procedure analogous to the traffic light situation, animals are rewarded with food pellets for completing a fixed ratio of 100 responses in the presence of a green light. Superimposed upon this baseline performance are 5-second presentations of a yellow warning light terminated by a red light in the presence of which all responses are punished with electric shock. When the yellow light is introduced late in the sequence (e.g., after 93 responses have been completed), response rates increase and the 100-response ratio is completed before the 5-second yellow light times out. When the yellow light appears early in the sequence (e.g., after 73 responses) a marked decrease in response rate is observed with cessation of responding before onset of the red light. The sensitivity of components of this risk-taking performance to pharmacological toxicants is reported and psychophysical assessment of relevant sensory-motor effects described.

The rate of blood ethanol disappearance was significantly increased in lactating rats compared to virgin controls and parturient rats that had their offspring removed in birth. Liver but not kidney size was also increased in lactating rats.

Trichloromethane (TCM) has been identified as an important contaminant of drinking water. TCM was evaluated for possible behavioral effects in the offspring of mice treated throughout the reproductive period. Male and female albino mice were gavaged with vehicle (Emulphor: saline) or 31.1 mg/kg/day for 21 days prior to mating, throughout mating (21 days or until a vaginal plug was detected) and the dam was continued with daily gavage throughout gestation and lactation. The pups were also gavaged daily with the same dose beginning on Day 7. Five TCM and five control litters were used for this study. On the day of birth each litter was reduced to 8 pups. For the next 15 days, 3 pups from each litter were randomly selected each day for evaluation on a battery of tests of neurobehavioral development. The scoring system for this test battery was developed for this study. On Day 17 motor performance for all pups was evaluated using the latency to right themselves on an inverted screen. On Days 22 and 23 they were evaluated on a one-trial passive avoidance learning task. No consistent significant differences were observed in any of the measures between TCM and vehicle treated groups.

The hippocampal afterdischarge (AD) has been suggested as an index of toxicant-induced CNS change [1]. The present experiments report raised AD thresholds, decreased AD durations, shorter post-stimulation latencies to AD onset, decreased numbers of AD spike complexes and increased numbers of spikes/complex following alcohol administration. Results are discussed in light of single-unit data concerning alcohol effects upon hippocampal cells, and the biphasic effects of alcohol upon behavior.

The need for a sensitive and reliable screen to assess environmental agents for potential behavioral and neurological toxicity is discussed. Factors involving strategy, choice of animals and doses, route of administration, duration of study and requirements for the selection of neurobehavioral tests are also evaluated. The primary emphasis concerns the need for standardization and validation of neurobehavioral tests to be used in neurotoxicology. It is suggested that test validation be accomplished by comparing the observed results of known neurotoxicants in animal models which are chosen to predict effects based on reported human symptomatology. As a means of demonstrating how test validation is used in our laboratory, data from a number of experiments concerning the effects of a variety of chemical agents on three measures of motor functioning were discussed. The neurobehavioral effects of acrylamide, and agent known to produce "dying-back" axonopathies, were assessed using separate techniques presumed to measure hindlimb and forelimb functioning and general motor activity. The prediction that acrylamide will first decrease hindlimb functioning, while decreasing forelimb grip strength and motor activity at higher doses, was confirmed. The validity of the hindlimb measurement was supported using a neurotoxicant, carbon disulfide, known to affect motor functioning in a manner similar to acrylamide. The validity of the forelimb technique was shown indirectly using normative data collected from rats of both sexes tested at various ages, i.e., males were stronger than females and grip scores changed as a function of age. The relative sensitivities of the fore- and hindlimb measurements were found to be approximately the same when used to assess the effects of known muscle relaxants, such as phenobarbital and chlordiazepoxide. Finally, it was predicted and confirmed that an environmental agent believed to affect behavior secondarily to effects on other organ systems would affect all measures of motor functioning at approximately the same dose.