Neurobehavioral toxicology最新文献

Sixty Sprague-Dawley derived primaparous rats were administered Luminal (sodium phenobarbital) subcutaneously in doses of either 80 mg/kg, 40 mg/kg, or 0 mg/kg (saline) on Days 9-21 of gestation. The two drug groups delivered litters significantly later with evidence of increased resorption at the higher dose. The higher dose offspring were lighter in weight at birth and at adulthood, but not at weaning. The lower drug dose offspring were developmentally accelerated compared with the other two groups. Acquisition of a conditioned avoidance response (CAR) was negatively correlated with increased drug dose. In appetitive operant paradigms, saline offspring received more reinforcements on fixed ratio sequential schedules, and the lower drug dose offspring received significantly fewer reinforcements than either of the other two groups on an FR-concurrent schedule. Both groups of drug offspring were able to obtain their reinforcements with a lower expenditure of effort than the saline offspring. The higher drug dose offspring made significantly more incorrect (early and late) responses on a schedule which rewarded a delayed response (DRL).

A step by step procedure is described for programming the method of Bliss for analyzing nominal dose-effect data for use with an advanced programmable calculator. A comparison of the results using this method with the results of others shows a good correspondence.

Twenty-two pregnant Sprague-Dawley rats were maintained on methadone hydrochloride solution (14 mg/kg/day, PO, ad lib) throughout gestation, or served as prenatal controls with equal intake of tap water. Within 48 hr of birth 129 pups were cross-fostered to dams of postnatal control or methadone (27 mg/kg/day, PO, ad lib) status. A significant increase in stillbirths occurred among prenatal methadone litters. Disturbed maternal behavior sometimes developed when a dam was switched from prenatal control to postnatal methadone or vice versa. Foster pups of such females showed long-lasting growth retardation and less emotionality in Open Field trials as adults. They were less active on Day 28 in a circular path test, but when tested after Day 65, they were more active. Pups exposed to methadone both pre- and post-natally were lest active in initial Open Field tests (both on Day 28 and after Day 65) of all treatment groups. No severe withdrawal symptoms were noted in pups at birth or weaning. The effect of methadone on growth, emotionality and activity level was mild compared to the effects of drug-induced maternal disorganization.

Activity measurements are expected to have widespread use in toxicity testing. The multifaceted nature of motor activity will directly influence the selection of a measurement technique since the relative contribution of various motor acts to any particular measurement will depend upon the detection method. Because of the apparatus-dependent nature of motor activity measurements, it is recommended that consideration be given to how accurately the various devices measure locomotor activity. In the present paper, two types of body movement will be considered as locomotor activity: ambulation (horizontally directed movement) and rearing (vertically directed movement). Discussion focuses on the various methods currently used to record motor activity, the various components of motor activity which are likely to be recorded, and the advantages and disadvantages of these techniques for the measurement of locomotor activity. Finally, consideration is given to studies which have compared treatment effects on motor activity derived from two or more measurement techniques.

Distal axonopathy is the most common form of toxic injury to the peripheral nervous system. Morphological studies of the experimental distal axonapathies produced by acrylamide monomer and hexacarbons have lead to a reappraisal of the dying-back hypothesis. These studies have also provided a rationale for many of the clinical findings in humans with distal axonopathies, and have been especially helpful in elucidating the effects of axonal neurotoxins on the central nervous system.

Neonatal rats were exposed to lead (Pb) from parturition to weaning via the milk of dams which consumed 0 (tap water), 0.02% or 0.2% PbAc2 solutions. To determine if this regimen altered physiological and neurobehavioral development, responses to a battery of sensory-motor tests were evaluated during maturation and as adults. The tests were: visual evoked responses (VER), temperature regulation, maximal electroshock seizure patterns, reflex patterns, and neuromuscular performance. Overall results revealed that the Pb-exposed group compared to controls exhibited delayed maturation, altered developmental patterns and long-term CNS disturbances. Additionally, low-level strychnine administration during development caused additive interactions with both Pb groups, uncovering subtle effects of toxicant exposure. These sensitive and quantifiable techniques proved useful for assessing CNS functioning following perinatal insult, and except for the VER, are simple to conduct and cost efficient because they require a minimal amount of personnel training, equipment cost and time invested per animal. These screening tests also suggest further areas of study and may indicate the mechanism(s) responsible for the deficit.

Rats and rhesus monkeys were trained under a multiple schedule, the components of which were random ratio schedules for food presentation and for shock presentation. The discriminative stimulus for the shock presentation component was a pure tone for the rats and a light for the rhesus monkeys. In the test session under the extinction condition for the shock presentation component, the intensity of the discriminative stimulus was successively either decreased by fixed units when the conditioned suppression was observed or increased when the conditioned suppression was not observed. The levels finally oscillated within a narrow range around the threshold. The auditory thresholds of rats were increased by intramuscular administration of quinidine at 20 mg/kg and also by repeated intramuscular administration of kanamycin at 250 and 500 mg/kg/day. In rhesus monkeys, visual thresholds were raised by application of pilocarpine at 0.02-0.16 mg/kg to the eyes and also by subcutaneous administration of LSD-25 at 4-8 micrograms/kg in one monkey and at 20-30 micrograms/kg in another. The method used for tracking the animals' sensory thresholds was sensitive enough to test the selective effect of the drugs and was also a relatively easy way to obtain a stable behavioral baseline for experimental purposes.

A procedure has been developed to measure the repeated acquisition of serial position sequences and to study the effects of drugs and toxic chemicals on the behavior generated by the procedure. Thus far experiments using the procedure have shown: (1) Performance schedules generate lower error rates than corresponding acquisition schedules: (2) Addition of a reset contingency further decreases errors under both performance and acquisition schedules: (3) Chained acquisition and performance schedules generate lower error rates than corresponding tandem acquisition and performance schedules: (4) Chained acquisition and performance schedules produce behavior that usually is more sensitive to drugs than corresponding tandem acquisition and performance schedules: (5) Acquisition schedules produce behavior that usually is more sensitive to drugs than corresponding performance schedules: and (6) Lead is an exception in that it produced clearer effects under a chained performance schedule with a reset contingency than under a corresponding acquisition schedule. The greater sensitivity to drug effects of behavior under acquisition schedules than behavior under performance schedules and of behavior under chained schedules may be a function of the baseline error rates, rather than the behavioral processes of acquisition, performance, and stimulus control.

In the present state of science no morphological or chemical changes may be detectable at a time when behavior is profoundly disturbed, as in schizophrenia. Until we are reassured to the contrary, we must assume that exogenetic intoxication can produce changes detectable only as behavioral changes. Therefore behavioral toxicology must be studied. In contrast to toxic manifestations such as lethality or carcinogenicity, which tend to be unequivocal and irreversible, behavioral changes are like physiological changes in that they are quantitative, changing in time, and relate to variables with a considerable range of normal variability. An experiment on behavioral teratology in mice is described and the results used to illustrate the limits of the possible in behavioral toxicology. From reported and observed variability it is surmised that changes that occur in as many as 1 per 100 of the population or average as large as a 10% decrement will still be too small to be detected by direct experiment. Such risks are frequently unacceptable. Reasons are given for hoping that epidemiological studies may be able to supplement experimental toxicological studies to provide a better assessment of risk of small impairments or rare susceptibility.

A series of experiments was performed to examine the utility of using the properties of artifically induced seizures as indices of the toxic effect of CO upon the CNS. The two behavioral seizure models tested, 6 Hz ECS and pentylenetetrazol, were unable to differentiate between exposed and unexposed animals, even at severe concentrations of CO (55% HbCO). On the other hand, the hippocampal afterdischarge (AD) proved to be at least as sensitive as the visual evoked potential method. There was a CO concentration-dependent shift in the AD type. CO increased the probability of occurrence of post-ictal depressions (PIDs) without rebound ADs, an event never seen in control animals. CO also decreased the spike frequency within ADs in a dose-dependent manner.