Neurotoxicology and teratology
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Neurotoxicol Teratol · Jan 2000
Comparative StudyAdaptation of a primate operant test battery to the rat: effects of chlorpromazine.
The National Center for Toxicological Research (NCTR) Operant Test Battery (OTB) has been used extensively in rhesus monkeys to characterize the effects of drugs and toxicants on the performance of tasks designed to model several cognitive functions. Recently, the majority of the OTB tasks have been adapted for use in rats. The current study is the first to examine the effects of a prototypic pharmacological agent previously assessed in monkeys on rat OTB performance. ⋯ This pattern of sensitivity was very similar to that obtained when chlorpromazine was tested in monkeys performing the OTB. These data thus suggest that operant tasks designed to model cognitive functions in monkeys can also be used in rats, and that the effects of chlorpromazine on the performance of these tasks may be predictive of results obtained with monkeys. Further characterization of the rat OTB using prototypic pharmacological agents will further determine the extent to which drug effects on rat OTB performance can be generalized to primates.
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Neurotoxicol Teratol · Nov 1998
Comparative StudyHeart rate variability in neonatal rats after perinatal cocaine exposure.
Pregnant rats received saline once daily (Control QD) or twice daily (Control BID), cocaine 2 mg/kg IV daily (COC QD) or twice daily (COC BID) throughout gestation beginning on gestational day 4. The treatment was continued in nursing mothers until postnatal day 7. All studies were performed in their offsprings on postnatal days 1 and 7. ⋯ Our results indicated that there were normal developmental changes in HRV consistent with continued postnatal development of autonomic nervous system. Perinatal cocaine exposure appeared to modify these changes. The specific autonomic mechanism for the cocaine effect may be a decline in parasympathetic activity and a concomitant change in sympathetic activity.
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Neurotoxicol Teratol · May 1996
Review Comparative StudyDevelopmental neurotoxicity of PCBs in humans: what do we know and where do we go from here?
The potential neurotoxicity of PCBs was first recognized in 1968 when a number of Japanese people became ill after ingesting rice oil that was contaminated with PCBs during the manufacturing process (Yusho). Later a similar exposure occurred in Taiwan (YuCheng). Children born to Taiwanese mothers who consumed PCB-contaminated rice oil were followed and a number of developmental abnormalities, including lower body weight and height, higher activity levels, greater incidence of behavior problems, and lower IQ scores, were observed. ⋯ However, it is not clear that these shortcomings can explain the discrepancies between their findings and those of Rogan and Gladen. Other possible explanations include differences in exposure levels or PCB congener patterns between the two cohorts, differences in sociodemographic variables between the two cohorts, or other problems inherent in trying to detect subtle neuropsychological deficits at exposure levels that are near the threshold for effects. Hopefully, several new studies that are currently underway will help to resolve the uncertainties regarding the risks of perinatal PCB exposure that have been created by the conflicting results of these early studies.
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Neurotoxicol Teratol · May 1996
Review Comparative StudyEpidemiologic perspective of the developmental neurotoxicity of PCBs in humans.
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Neurotoxicol Teratol · May 1996
Review Comparative StudyCan epidemiological studies discern subtle neurological effects due to perinatal exposure to PCBs?
What conclusions can be drawn concerning the potential neurological effects of perinatal exposure to either PCBs, or PCBs and other fish-borne contaminants? First, by their very nature epidemiological studies are limited in their ability to detect subtle associations--including possible links between exposure to low levels of environmental contaminants and disease. As stated by Dr. Schantz, both Rogan and the Jacobsons report small changes in motor and cognitive behavior--typically less than one-half of a standard deviation--and only in the most highly exposed children. ⋯ In light of the above statements, future epidemiological studies should focus on highly exposed susceptible populations such as occupationally exposed workers or the aged. Results from these studies would provide important information on the risk of perinatal or adult exposure to PCBs in susceptible populations, although generalization of results obtained in these populations to the general population may be fraught with difficulties. Finally, because of the limitations of epidemiological studies, particularly those studying fish-eating populations, future risk assessments should depend more heavily on laboratory derived data, including studies in nonhuman primates exposed to environmentally relevant mixtures and relevant doses of PCB congeners and other known or suspected neurotoxicants.