Neurobehavioral toxicology最新文献

Male and female rats of the Fischer Strain were dosed with 550 mg/kg of benzene or corn oil vehicle on Days 9, 11 and 13 postpartum. The spontaneous motor activity of benzene exposed rats (males and females) was found to be elevated when tested at 100-130 days of age. When challenged with various doses of d-amphetamine (0.3-3 mg/kg), the benzene exposed rats were found to be less sensitive to the motor activity increasing effects of the drug. In a subsequent test to measure specific components of exploratory activity in an operant chamber (nose-poking, wall rearing, lever touching), female rats exposed to benzene were found to emit fewer rearing responses. Body weights and performance in a battery of tests to assess neurobehavioral toxicity (Days 45, 60 and 100 postpartum) were not affected by postnatal exposure to benzene. These data indicate that postnatal exposure to benzene can produce significant alterations in the motor activity of rats when tested during adulthood and the type of effect depended on the procedure used. Changes in the sensitivity of benzene exposed animals to d-amphetamine suggest long-term alterations in catecholaminergic function.

Fifteen rats in which responding under the Sidman avoidance schedule had been established were first exposed to air for 4 hr, then randomly to 350, 750 or 1,500 ppm of toluene vapor for 1, 2 or 4 hr, following which the effects on lever pressing behavior were investigated for 80 min after the termination of toluene exposure. The effect of concentration, exposure duration and test period on lever pressing of toluene was revealed clearly in the test. Using the technique adopted in this experiment, one could be determining the minimal effective exposure condition in terms of toluene concentration and exposure duration is 1,500 ppm for 2 hr. These findings suggest the usefulness of this technique in assessing the behavioral toxicity of toluene.

Previous studies have shown that the putative excitatory neurotransmitters and neurotoxins, glutamate (Glu) and aspartate (Asp), destroy neurons in the brains of various animal species when administered orally by feeding tube. It has been argued, however that Glu and Asp are safe for human use as food additives since tube feeding is not a natural means of oral intake and efforts to demonstrate the brain damage in animals from voluntary ingestion of Glu or Asp have yielded negative results thus far. Here we demonstrate that weanling mice will voluntarily ingest large enough volumes of aqueous solutions containing Glu or Asp (or both) to sustain conspicuous hypothalamic damage. Certain deficiencies in the design of prior voluntary intake studies may explain the failure of others to demonstrate brain damage from voluntary ingestion of these excitatory neurotoxins.

Gravid rats were treated with methadone, 10 mg/kg/day, or vehicle, from day 5 of gestation to term. The offspring were nursed by foster mothers receiving either methadone or vehicle to form 4 groups: (A) methadone during gestation and lactation, (B) methadone during gestation, (C) methadone during lactation, and (D) no drug treatment. Brain monoamines and metabolites were examined at 21 days of age and found to be decreased in groups A and B. Animals treated comparably to group B and sacrificed at 90 days of age showed no abnormalities in brain monoamines excepting a decrease in dopamine metabolites in limbic areas. Another group treated in utero with methadone was tested at 90 days fo age for shuttle-box avoidance acquisition using massed trials. Methadone-exposed subjects exhibited more avoidances, escapes and intertrial shuttles than controls by the third day of training. These results suggest that subtle but lasting changes in limbic dopamine functions as a consequence of fetal exposure to methadone may make rats hyper-responsive in a massed-trial avoidance procedure in the shuttle-box.

Few experiments have been carried out to evaluate the effects of toxic industrial substances such as the solvents on operant behavior. Laboratory rats trained in a mult FR DRL reinforcement schedule showed a differential impairment in performance when exposed to various doses of paint thinner in the experimental chamber, the FR performance being more sensitive to the solvent than DRL responding. Another study of rats working under a FI schedule suggested that the effects of paint thinner are rate-dependent, a finding which suggests a similarity of thinner with the amphetamines in regard to the behavioral effect. Two other experiments addressed to the behavioral effects of chronic exposure to the solvent showed a decrease in locomotor activity and an impaired acquisition of a complex temporal discrimination task in laboratory rats exposed to paint thinner during four, eight of sixteen weeks. These findings are suggestive of brain dysfunction associated with thinner inhalation but further experiments are needed for more definite conclusions.

Rats were exposed to paint thinner twice a day for a period of 10 minutes on Days 1 through 30 of postnatal life. The subsequent effects upon physical development, swimming ability and escape latency from water were evaluated. Maturation of swimming behavior and general physical development were delayed about 2-4 days in the experimental animals compared with non-exposed littermate controls. The results of these experiments suggest that exposure to this organic solvent during the early postnatal period interferes with the development of the cortico-subcortical neural structures underlying swimming and locomotion.

Sic male rats were trained on a variable interval 5 min schedule of reinforcement. Each rat, serving as its own control, was given itraperitoneal (IP) and intramuscular (IM) injections of 1, 3, 5, and 10 mg/kg l-naphthyl N-methylcarbamate (carbaryl). There were significant decreases in response rate following 3, 5, and 10 mg/kg IP injections and 5 and 10 mg/kg IM injections of carbaryl.

Inbred audiosensitive mice exposed to a prolonged auditory signal recovered and remained refractory to further audiogenic seizures as long as the signal was continued. Susceptibility to audiogenic seizures returned upon cessation of sound. The rate of return was the same whether the sound stimulus was brief or prolonged. In a small proportion of test animals, which failed to become fully refractory, the continuing auditory stimulus proved lethal. Mice maintained in the post-seizure refractory state were fully susceptible to Metrazol-induced seizures.

Young rats were treated with thinner inhalations (50 and 100 p.p.m., v/v). The brains of treated and control animals were studied with standard techniques of light and electron microscopy and with ultrastructural cytochemical method for localization of RNA. No alterations were found in the group treated with a single session of inhalation, irrespective of the dose. Animals treated with 10 or 20 sessions showed altered neurons in cerebral cortex, caudate nucleus, hypothalamus and cerebellar cortex. More frequent alterations were: small nucleoli with loss of their reticular structure and a marked decrease of their normal granular component; diminution of perichromatin fibrils and of ribosomes. In the animals treated with high doses of thinner (20 sessions, 100 p.p.m.) a small number of neurons show an increased amount of lysosomes, autophagosomes and neurofibrillar hypertrophy. These results suggest that thinner inhalation causes an initial impairment of gene transcription and of RNA processing followed by neuronal degeneration.

Many previous studies have examined the effects of unconjugated bilirubin on cerebral energy metabolism. The results have been equivocal largely because the samples for assay included contiguous less affected tissue. The present study was undertaken to obviate this problem. Kernicteric Gunn rat cerebella were sectioned, freeze dried, and Purkinje cell rich layers prepared, as well as adjacent molecular and granular layers. These layers were assayed, along with suitable controls, for glucose, glucogen, ATP, and phosphocreatine. ATP and phosphocreatine were decreased in the Purkinje cell rich layer only; molecular and granular layers were unaffected. Glucose and glycogen were increased in all three layers. These results support the concept that in vivo, bilirubin exerts its toxic effect by uncoupling oxidative phosphorylation.