Neurobehavioral toxicology最新文献

Occupational exposures to neurotoxic chemicals have produced large outbreaks of illness in chemical and pesticide workers worldwide. Outbreaks of occupational neurologic disease in the United States have included (1) the Kepone episode in Hopewell, Virginia, in which 76 workers at a pesticide plant producing the chlorinated hydrocarbon insecticide, Kepone, developed a previously unrecognized syndrome of nervousness, tremor, ataxia, weight loss, opsoclonus, pleuritic and joint pain, and oligospermia; (2) an outbreak of 104 cases of autonomic neuropathy in polyurethane foam workers in Marblehead, Massachusetts, manifest principally by urinary bladder dysfunction, which followed exposure to a new catalyst, dimethylaminopropionitrile (DMAPN); and (3) an outbreak of acute mixed motor and sensory neuropathy in 48 plastic fabric workers in Columbus, Ohio, exposed to the solvent methyl butyl ketone (MBK). These outbreaks underscore the vulnerability of chemical workers to neurotoxins. In addition, occurrence of these large, easily detectable epidemics suggests that many more smaller clusters and single cases of neurologic disease of undetermined origin, particularly in younger adults, may be caused by exposure to occupational or to other toxic chemicals. Detection of the etiology of chemically induced neurologic illness requires a high index of suspicion and careful ascertainment of occupational history.

The analysis of selected data on differential behavioral tolerance to drugs and other chemicals leads to a series of tentative methodological proposals with potential interest for the purposes of toxicology. These data show a wide range of different relations between tolerance induced by continued exposure to treatment per se and tolerance dependent on specific treatment-behavior interactions, such as behavioral testing in the treatment state and unfavorable consequences on reinforcement density of response changes induced by treatment. Consequently, when tolerance phenomena occurring with a particular type of treatment deserve an in-depth analysis, a sequential strategy should assess (i) critical factors in short-term compensation for behavioral deficits (acute behaviorally augmented tolerance), (ii) relations between sensitization and tolerance phenomena (particularly in the case of agents with long-lasting and/or cumulative physiological-biochemical effects), with special regard to tolerance development in the absence of measurable changes in the lower dosage ranges, and (iii) factors responsible for behaviorally augmented tolerance in medium-and long-term experiments. The latter analysis may require the investigation of different relations between time of treatment and time of testing, and different treatment-induced changes in reinforcement density. Specific and non-specific transfer of coping responses across situations must also be considered, as well as changes in response topographies, interindividual differences in rate of tolerance development as a function of size and direction of the original treatment changes, and several other cues which can facilitate the understanding of the phenomena observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Many neurotoxic chemicals of environmental significance can be conveniently classified according to their cellular site of action in the nervous system. This paper considers neurotoxins which damage the nerve cell body (neuronopathy), its axonal process (axonopathy), or the myelin sheath which segmentally enwraps the myelinated axon (myelinopathy). Each of these three conditions can be reproduced in experimental animals for study of the mechanisms and consequences of neurotoxic damage. Detailed morphological examination of toxic distal axonopathies have stimulated biochemical studies which promise to yield a precise explanation of the molecular basis for this common type of neurotoxic disease. It seems possible that a precise description of the molecular basis for toxic distal axonal degeneration is within sight.

Deprivation of magnesium ion in the diet caused a significant decrease in whole brain acetylcholine content. At the reginal level, the most pronounced effect was seen in the corpus striatum, diencephalon and cerebellum. The rate of depletion and recovery varied from region to region, and what appeared to be a return to normal acetylcholine in whole brain was the total of regions either higher or lower than control. The data presented here suggest that a positive relationship exists between the lowered cholinergic activity in the corpus striatum and increased nocturnal spontaneous motor activity.

Rats were exposed on gestational day 15 to 125 r X-irradiation, a treatment known to severely alter brain morphology. At 4-6 weeks of age the behavior of these animals was studied using two methods: (1) measurement of circadian locomotor activity, (2) photographic analysis of behavioral acts. The circadian locomotor activity of irradiated rats was similar to that of controls tested individually or as groups in a residential unit. After morphine sulfate, 2 mg/kg, the increase in locomotor activity was greater for the irradiated than control groups. Successive frames of photographic film were analyzed to determine the frequency, duration, sequencing of behavioral acts. No significant differences were present in these parameters of behavioral acts of control and irradiated rats. After morphine, irradiated rats showed a greater increase than controls in frequency and initiations of some behavioral acts, and these acts were more randomly dispersed in the sequences of acts. In this experiment activity was little affected by an agent which severely alters brain morphology, but the latent behavioral effects of the permanent brain damage became manifest, when the testing situation included challenge with a low dose of a drug which caused hyperactivity.

Prenatal exposure of rats to marihuana extract impaired Rotarod performance in female offspring but did not affect inclined plane, spontaneous alternation, learning/memory, or open-field performance.

Procedural variables are crucial in using taste aversion as a measure of lead toxicity. Rats were given saccharin and water to drink while ingesting a diet containing lead acetate (PbAc). Rats showed high preference for saccharin (over water) before lead was introduced. Saccharian preference fell during PbAc ingestion and rose when PbAc was removed from the diet suggesting that saccharin preference may correlate with the physiologic action of the toxicant. When saccharin was introduced simultaneously with PbAc aversion was almost total, but recovered with continuous PbAc exposure. When saccharin was introduced after the start of PbAc exposure saccharin aversion diminished with the duration of presaccharin PbAc exposure.

Learning or performance of an operant discrimination task by laboratory rats in Skinner boxes was studied as a function of subchronic treatment with polybrominated biphenyl (PBB) (1.0 mg/kg, 3.0 mg/kg or 6.0 mg/kg for 20 days). Acquisition of the discrimination task was similar for experimental and control rats at each dose level. Response times were slower for the 1.0 mg/kg rats but were like controls for the 3.0 and 6.0 mg/kg animals. Extra responses occurring in the absence of auditory discriminative stimuli increased significantly for the 1.0 mg/kg rats (hyperactivity), were no different from controls for the 3.0 mg/kg rats and decreased significantly for the 6.0 mg/kg animals (CNS depression). The weights of PBB animals did not differ significantly from controls. Analyses of brains and plasma by electron capture gas chromatography yielded detectable levels of PBB as long as 10 months following the last PBB administration. PBB in brains and plasma varied directly as a function of dose administered.

Rats were given PBB orally at 1, 3, and 6 mg/kg (or vehicle as control) daily for 20 days. Some animals were sacrificed immediately while the food intake of remaining animals was limited to attain and maintain 80% of normal body weight. No effect of PBB upon body weight was observed for any of the dose levels employed. Immediately after dosing, liver/body weight ratios were 110% of controls for the 1 mg/kg group and 152% for the 3 and 6 mg/kg groups; after weight reduction for 2-6 months liver/body weight ratios for all 3 dose groups were 160-170% of controls. In the absence of body fat, most tissues exhibited dose-dependent retention of PBB 2-6 months after dosing with highest levels in liver followed by kidney. In 6 mg/kg rats weight-reduced for 6 months, liver AHH activity was 613% of controls; in rats sacrificed immediately after dosing, liver AHH activity was dose-related but appeared to reach maximal value at the 3 mg/kg dose. Both calcium binding to synaptic plasma membranes and calcium uptake by intact synaptosomes was significantly reduced in the brains of 1 mg/kg PBB rats, but not affected in preparations from 3 and 6 mg/kg animals.