Search PubMed⌕ Search

Biomedical subjects

E D Levin

Publications and source records attributed to E D Levin.

143 records · Page 8Linked to original sources
PubMedDate not supplied

Long-term effects of chronic postnatal lead exposure on delayed spatial alternation in monkeys.

Two cohorts of monkeys chronically exposed to lead during the first year after birth and their controls were tested during adulthood for choice accuracy on a learning and memory task, delayed spatial alternation (DSA). Neither cohort showed significant lead-related deficits, as had been seen in a previous experiment with monkeys exposed to similar chronic levels of lead during the first year with an additional high pulse given five-six weeks after birth (18,19). On the contrary, the lead-exposed monkeys in the present experiment actually performed slightly better than controls. In the previous (pulse-chronic) study, the deficit occurred at short intertrial delays, suggesting an attentional rather than mnenomic deficit. A lead-induced decrease in attentiveness could also explain the present results. The lower level lead intoxication may have decreased attentiveness to a lesser degree, so that the monkeys were less susceptible to irrelevant stimuli and performed better.

Animals↗
PubMedDate not supplied

Effects of perinatal PCB exposure on discrimination-reversal learning in monkeys.

Monkeys exposed to PCB mixtures during gestation and lactation were tested on two-choice discrimination-reversal learning (DR). In Experiment 1, offspring of mothers fed 1.0 ppm Aroclor 1248, and offspring born 1.5 years after maternal exposure to 2.5 ppm Aroclor 1248 ended did not differ from controls on spatial, color or shape DR problems. In Experiment 2, offspring of mothers fed 0.25 or 1.0 ppm Aroclor 1016 and offspring born 3 years after maternal exposure to 2.5 ppm Aroclor 1248 ended were tested on the same spatial, color and shape problems, but a spatial problem with color and shape as irrelevant cues was inserted after the initial spatial problem. Performance of the high dose Aroclor 1016 offspring was impaired on the initial spatial problem, and facilitated on the shape problem. Performance of the Aroclor 1248 postexposure offspring was facilitated on the shape problem. This apparently facilitatory effect may represent a failure of PCB-exposed monkeys to learn the irrelevancy of the shape cue when it was initially presented.

Adipose Tissue↗
PubMedDate not supplied

Neurobehavioral toxicology of halothane in rats.

Halothane, a commonly used general anesthetic, is considered to be relatively safe for that purpose. Chronic exposure, however, has been found to cause long-lasting damage to neural structure and impairment of behavioral function. In rats, behavioral alterations are particularly evident after developmental exposure, but they can also be seen with adult exposure, especially when halothane is given during the period of neural regrowth following a brain lesion. The pattern of neural damage includes retarded synaptogenesis, impaired dendritic branching and disruption of organelle structure. The behavioral syndrome includes learning impairment, decreased exploratory behavior and decreased nociceptive reactivity. In general, the neural pathology is more pronounced and more easily discernible than the behavioral effects. Neural damage, particularly to the hippocampus, can be clearly seen at points when behavioral impairments have not been found. This demonstrates that in some cases changes in neural structure can be more sensitive indicators of toxic damage than behavioral dysfunction. Halothane exposure has proved to be quite useful as an experimental tool in the study of neural and behavioral recovery after brain lesions. For example, after unilateral entorhinal cortical lesions, behavioral recovery and reactive synaptogenesis occur contemporaneously. It has not been demonstrated whether the behavioral recovery is due to this reinnervation. Postlesion halothane exposure almost completely suppresses reactive synaptogenesis, however, behavioral recovery of T-maze alternation behavior occurs in the halothane-treated rats as well as in controls. This suggests that recovery of spatial performance after such a lesion is not due to recovery of innervation in the dentate, but to some other process such as other neural systems taking over the functions lost with the brain lesion. The studies reviewed highlight the dangers of halothane exposure, especially during development or when recovering from brain injury. They also provide a good case study for comparing the relative sensitivity of morphological and behavioral measures in toxicology and point to the potential use of halothane as an experimental tool for examining the relationships between neural structure and behavioral function.

Animals↗
PubMedDate not supplied

Use of the lesion model for examining toxicant effects on cognitive behavior.

It is often beneficial to use a model to help understand unknown effects and relate those effects to an existing body of knowledge. In much of the early development of behavioral toxicology, the pharmacological model has served as a valuable theoretical guide, especially with regard to dosing and kinetic parameters. However, as with any model, it has certain limitations. The lesion model has complementary features which provide valuable insights into the behavioral effects of toxicants. This is particularly true for effects which persist long after the end of toxicant exposure. There is much literature describing effects of brain lesions on behavior. By comparing results from toxicology studies to those of lesion studies, one can take advantage of this trove of information to gain a better insight into the possible loci of toxic effects, and to identify tests which would be useful in further describing the nature of the toxic effects. In this article, we examine the theoretical and practical utility of the lesion model. Examples are given showing how it has proven useful in interpreting the cognitive effects of exposure of monkeys to lead and polychlorinated biphenyls (PCBs). These exposures produced syndromes that closely resemble the effects of lesions in the frontal cortex or limbic system.

Aging↗
PubMedDate not supplied

Prenatal nicotine exposure and cognitive performance in rats.

In humans and animal models there is evidence that prenatal nicotine exposure causes lasting deficits in cognitive performance. The current study examined the cognitive effects of prenatal exposure of rats to 2 mg/kg/day of nicotine. This dose did not cause significant deficits in maternal weight gain, offspring litter size, or pup weight. The control offspring showed the normal ontogeny of spontaneous alternation from near chance (50%) performance to 80%-85% alternation. In contrast, the nicotine-exposed rats had the opposite progression with abnormally high alternation on days 22-30 and abnormally low alternation on days 35-52. Acquisition of choice accuracy performance on the radial-arm maze (RAM) was not altered in a major way by nicotine exposure. Minor nicotine-induced changes in choice accuracy were seen during the initial trials of acquisition. The nicotine exposed female offspring had a significantly longer response duration. Prenatal nicotine exposure did significantly alter the effects of subsequent drug challenges on choice accuracy performance. The nicotine-exposed male offspring were significantly more responsive to the amnestic effects of the nicotinic antagonist mecamylamine. In a subsequent challenge, the effects of the beta-adrenergic antagonist propranolol were examined. A significant dose-related impairment in choice accuracy was seen in the control rats. In contrast, the nicotine-exposed rats did not show any significant response to propranolol. This decreased responsiveness to adrenergic challenge parallels the reduction in adrenergic response to nicotine challenge we previously found in littermates to the rats of the current study. Prenatal nicotine exposure causes subtle alterations in cognitive performance that can be magnified by challenges of nicotinic and adrenergic systems.

Animals↗
PubMedDate not supplied

Development of treatments for toxicant-induced cognitive deficits.

A wide variety of toxicants have been found to impair cognitive function. Some such as lead, organophosphate pesticides, and polychlorinated biphenyls are quite widespread in the environment. Others such as alcohol, nicotine, and cocaine are widely used drugs of abuse. Many people are chronically exposed to these toxicants. Lasting cognitive deficits can result, especially after developmental exposure. Considerable research has been directed at developing pharmacological agents to treat the cognitive dysfunction associated with Alzheimer's Disease, Unfortunately, other types of cognitive dysfunction, such as toxicant-induced cognitive deficits, have not received the same degree of attention, despite the fact that they are quite widespread and may be more amenable to development of useful therapeutic treatments. Animal models can be particularly useful because the agents causing these deficits are known. In addition, for a variety of neurotoxic compounds, information concerning the nature of the cognitive effect and mechanism of toxic action can help in development of treatments. Prevention of toxic exposure is ideal. Removal from the source of pollution after exposure can help, but for those who already carry the burden of persistent deficits, development of efficacious therapeutic treatments is a necessity.

Animals↗
PubMedDate not supplied

Attention as a target of intoxication: insights and methods from studies of drug abuse.

A symposium was convened to discuss recent developments in the assessment of attention and the effects of drugs and toxic chemicals on attention at the 17th annual meeting of the Behavioral Toxicology Society on May 1, 1999, in Research Triangle Park, NC. Speakers addressed issues including the methodology of assessing cognitive function, the neurobiology of specific aspects of attention, the dual roles of attention as a target of intoxication and as a mediating variable in the development of addiction to psychoactive drugs, the changes in attention that accompany neuropsychological disorders of schizophrenia, senile dementia of the Alzheimer type and attention deficit hyperactivity disorder, and potential therapies for these disorders. This article provides an overview of the objectives of the symposium, followed by summaries of each of the talks given.

Animals↗
PubMedDate not supplied

Rapid neurobehavioral analysis of Pfiesteria piscicida effects in juvenile and adult rats.

The estuarine dinoflagellate Pfiesteria piscicida is known to kill fish and has been associated with neurocognitive deficits in humans. We have developed a rat model to demonstrate that exposure to Pfiesteria causes significant learning impairments. This has been repeatedly seen as a choice accuracy impairment during radial-arm maze learning. Pfiesteria-induced effects were also seen in a locomotor activity test in the figure-8 apparatus. The current studies used the short-term radial-arm maze acquisition, the figure-8 activity test, and the functional observational battery (FOB) to assess Pfiesteria-induced neurobehavioral effects in adult and juvenile rats. In study 1, the neurobehavioral potency of three different Pfiesteria cultures (Pf 113, Pf 728, and Pf Vandermere) was assessed. Ninety-six (12 per group) adult female Sprague-Dawley rats were injected subcutaneously with a single dose of Pfiesteria taken from aquarium-cultured Pfiesteria (35,600 or 106,800 Pfiesteria cells per kilogram of rat body weight). One control group (N = 12) was injected with saline and one (N = 12) with aquarium water not containing Pfiesteria. All three of the Pfiesteria samples (p < 0.05) impaired choice accuracy over the first six sessions of training. At the time of the radial-arm maze choice accuracy impairment, no overt Pfiesteria-related effects were seen using an FOB, indicating that the Pfiesteria-induced choice accuracy deficit was not due to generalized debilitation. In the figure-8 apparatus, Pfiesteria treatment caused a significant decrease in mean locomotor activity. In study 2, the neurobehavioral effects of the Pf 728 sample type were assessed in juvenile rats. Twenty-four day-old male and female rats were injected with 35,600 or 106,800 Pf-728 Pfiesteria cells per kilogram of rat body weight. As with adult females, the juvenile rats showed a significant impairment in radial-arm maze choice accuracy. No changes in locomotor activity or the FOB were detected in the juvenile rats. Furthermore, there were no differences between male and female rats in the Pfiesteria-induced choice accuracy impairment. Pfiesteria effects on choice accuracy in the radial-arm maze in rats constitute a critical component of the model of Pfiesteria toxicity, because the hallmark of Pfiesteria toxicity in humans is cognitive dysfunction. Our finding that analysis of the first six sessions of radial-arm maze testing is sufficient for determining the effect means that this test will be useful as a rapid screen for identifying the critical neurotoxin(s) of Pfiesteria in future studies.

Aging↗
PubMedDate not supplied

Specificity of cognitive impairment from Pfiesteria piscicida exposure in rats: attention and visual function versus behavioral plasticity.

Pfiesteria piscicida is a toxic dinoflagellate that has caused massive fish kills in estuaries along the East Coast of the United States, and exposure of humans to toxic Pfiesteria has been associated with cognitive impairment. A visual signal detection task was used to determine the possible importance of attentional and visual processes in Pfiesteria effects on cognitive function. Adult female rats were trained to perform the signal detection task. After training, the rats were injected subcutaneously with fish culture water containing toxic Pfiesteria (35,600 or 106,800 cells of Pfiesteria/kg of rat body weight) or with (control) fish culture water containing no Pfiesteria. Effects of toxic Pfiesteria on maintenance of signal detection behavior were assessed for 2 weeks after treatment. Then, the signal-response contingencies were reversed. After the discrimination was reestablished on the reversed levers, the rats received a second dose of toxic Pfiesteria. The rats were again tested for 2 weeks, after which a second reversal was imposed. Pfiesteria did not affect behavior in the signal detection task during 2 weeks of prereversal testing after either exposure. However, a significant Pfiesteria-induced deficit emerged when the signal-response contingencies were reversed. These findings suggest that Pfiesteria-induced deficits emerge during periods of behavioral transition and not during performance of previously learned tasks.

Animals↗
PubMedDate not supplied

Prenatal cocaine and/or nicotine exposure in rats: preliminary findings on long-term cognitive outcome and genital development at birth.

Prenatal cocaine or nicotine exposure is associated with a variety of teratogenic effects. The current study was conducted to determine their effects alone and in combination on cognitive function and sexual differentiation. Pregnant Long-Evans rats (N = 19) were exposed to either cocaine (15 mg/kg/dose b.i.d. SC on GD 8-20); nicotine (4 mg/kg/day continuous SC infusion on GD 4-20); both nicotine + cocaine; or vehicle only. Birth weight and anogenital distance (AGD) were measured in all pups at birth. Learning and memory were tested in the Morris water maze (MWM) during prepubertal and pubertal ages in five daily consecutive sessions and a sixth session 1 week later and in the radial-arm maze (RAM) during adulthood. In the RAM, a drug challenge of the beta-noradrenergic antagonist propranolol (10-20 mg/kg) was given after acquisition training. Maternal weight gain was reduced 13-42% and offspring birth weight was reduced by 7-12% in all three exposure groups compared to controls. Cocaine decreased the AGD of males (2.68 mm) compared to 2.88 mm in noncocaine-exposed male pups (p < 0.025). A sex-selective cocaine effect was also seen after adjustment of AGD measurements for body weight. With this measure cocaine-treated females showed significantly (p < 0.05) greater AGD than those not exposed to cocaine. In the MWM, there were two types of trials: cued reference memory trials and uncued spatial working memory trials. On cued reference memory trials significant cocaine-induced latency deficits were seen on only the first session. On spatial working memory trials cocaine-induced latency deficits were seen throughout daily training on sessions 1-5, but not the retention session 6, 1 week later. During RAM acquisition, there were no significant differences in choice accuracy between exposure groups. Following propranolol challenge, deficits in choice accuracy were demonstrated in rats prenatally exposed to cocaine or nicotine. These rats did not show any response to propranolol, whereas the controls slightly improved their choice accuracy. The results of this study indicated that prenatal cocaine exposure altered long-term cognitive function under basal conditions in the MWM and drug challenge in the RAM, birth weight, and genital development. Cocaine-induced cognitive deficits were predominately in working memory rather than reference memory or long-term retention. Prenatal nicotine exposure was only observed to alter birth weight and cognitive function in response to propranolol challenge in the RAM.

Abnormalities, Drug-Induced↗
PubMedDate not supplied

Pfiesteria toxin and learning performance.

Pfiesteria piscicida is an estuarine dinoflagellate involved with fish kills along the east coast of the United States. We previously documented a radial-arm maze learning deficit in rats exposed to Pfiesteria that may be related to cognitive deficits seen in humans after accidental Pfiesteria exposure. The current study elucidated important behavioral parameters of this deficit. There were six dose groups. Forty (10/group) adult female Sprague-Dawley rats were injected (s.c.) with a single dose of Pfiesteria taken from aquarium-cultured Pfiesteria (35,600, 106,800, or 320,400 Pfiesteria cells/kg of rat body weight or a cell-free filtrate of the 106,800 cells/kg dose). One control group (N = 10) was injected with saline and one (N = 10) with aquarium water not containing Pfiesteria. Half of the rats in each group were tested on an 8-arm radial maze in a standard test room, and the other half were tested on the radial maze in a sound-attenuating chamber. In the standard maze room, there was a significant effect of Pfiesteria (p < 0.05) impairing choice accuracy improvement over the first six sessions of training among rats administered 106,800, 320,400, and the 106,800 cells/kg filtered sample. In contrast, there was no indication of an effect of Pfiesteria when the rats were tested on the same configuration radial maze in the sound-attenuating chamber. After 18 sessions of training in one room, the rats were switched for six sessions of testing in the other room and finally were switched back to their original room for three sessions. There was a significant Pfiesteria-induced deficit when the rats were tested in the standard test room but not when they were tested in the sound-attenuating chamber. When the Pfiesteria-exposed rats were initially switched from the sound-attenuating chamber to the standard test room they performed significantly worse than controls, whereas Pfiesteria-treated rats switched from the standard test room to the sound-attenuating chamber did not perform differently from controls. These results suggest that the Pfiesteria-induced learning impairment may result from the negative impact of distracting stimuli. At the time of the learning impairment, no overt Pfiesteria-related effects were seen using a functional observational battery and no overall response latency effects were seen, indicating that the Pfiesteria-induced choice accuracy deficit was not due to generalized debilitation. In the initial use of the figure-8 maze in this line of research, the rats in the same Pfiesteria treatment groups that showed significant deficits in the radial-arm maze showed greater declines in activity rates in a 1-h figure-8 locomotor activity test. Both the 106,800 and 320,400 Pfiesteria cells/kg groups showed significantly greater linear trends of activity decline relative to tank water-treated controls. This reflected an initial slight hyperactivity in the Pfiesteria-treated animals followed by a decrease to control levels. Pfiesteria effects in the figure-8 maze and in early radial-arm maze training may be useful in a rapid screen for identifying the critical toxin(s) of Pfiesteria in future studies.

Animals↗
PubMedDate not supplied

Behavioral evaluation of perinatal PCB exposure in rhesus monkeys: fixed-interval performance and reinforcement-omission.

Two experiments were conducted to examine the prolonged behavioral effects of perinatal exposure to polychlorinated biphenyls (PCBs, Aroclor 1248) in rhesus monkeys. Experiment I involved testing a group of three monkeys whose mothers had been fed 2.5 ppm PCBs in their diets both before and throughout gestation and nursing (concurrent exposure condition), and a group of three control monkeys whose mothers had received no added dietary PCBs. These offspring began testing at approximately 60 months of age. In experiment II the same group of female breeders which were fed PCBs in experiment I underwent a second round of breeding after being off the contaminated diet for an average of 20 months (postexposure condition). Additionally, another group of female monkeys underwent breeding while receiving concurrent exposure to 0.5 ppm PCBs in their diet. Control female monkeys received no added dietary PCBs. Four offspring from the 2.5 ppm postexposure condition, four from the 0.5 ppm concurrent exposure condition and five control offspring survived to begin testing here at approximately 40 months of age. All monkeys from experiments I and II were tested under a series of fixed-interval schedules of food reinforcement consisting of FI 30 sec (10 sessions) and FI 60, 300 and 600 sec (15 sessions each). Performance measures included overall response rate, index of curvature (IC) and postreinforcement pause (PRP). There were no consistent differences in FI performance between PCB and respective control groups except for a slightly though significantly lower IC in the PCB groups of experiment II under FI 300 and 600.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Long-term lead effects on the Hamilton Search Task and delayed alternation in monkeys.

Exposure of rhesus monkeys to lead during the first year after birth resulted in cognitive deficits when the monkeys were tested as adults (5-6 years of age). A pronounced lead-related deficit was detected in the test of Delayed Spatial Alternation (DSA), and a much less robust effect was detected in the Hamilton Search Task (HST). Both tests provided examples of "windows of sensitivity" to the effect of lead, where the behavioral criterion was challenging enough to elicit a deficit in lead-treated monkeys while still being within the capabilities of the controls. The lead-induced deficit in DSA was most pronounced after short intertrial delays, suggesting that the effect was probably not due to a mnemonic dysfunction, but rather may have been due to deficits in strategy or attention. The lose-shift type of error accounted for most of the lead-related DSA deficit, indicating that the lead-treated monkeys perseverated on an alternation strategy even when it was not rewarded. These results indicate that exposure to lead during the first year after birth can result in very long-term and possibly permanent cognitive deficits.

Animals↗
PubMedDate not supplied

Effects of zinc deficiency on lead toxicity in rats.

The effect of zinc deficiency on the toxicity of dietary lead in rats, as measured by body weight changes, tissue lead retention, and choice behavior in a complex maze was studied. Weanling rats were fed a zinc-free semipurified diet which was supplemented via drinking solutions with either 2 or 20 ppm zinc and 0, 10, or 100 ppm lead. During exposure, choice behavior was quantified in a radial maze. After a 3-week period on diet, the animals' physical development was assessed, and the retention of lead and zinc in bone and brain were determined by atomic absorption spectroscopy. Zinc deficiency slowed rats' weight gain, did not affect relative organ weights, increased the retention of lead in both calvarium and in brain, and reduced the accuracy of performance in the maze. Lead exposure at 100 ppm reduced body weight and increased relative organ weights, and reduced maze accuracy at both 10 and 100 ppm. Neither treatment affected the rats' running speed through the maze. Lead exposure and zinc deficiency exerted additive effects on body weight. The two treatments did not interact in the behavioral assay.

Animals↗
PubMedDate not supplied

The effect of pre- or postnatal lead exposure on Hamilton Search Task in monkeys.

Rhesus monkeys were exposed to low, chronic levels of lead acetate either pre- or postnatally. Considerable neural and behavioral evidence indicates that the hippocampus is preferentially affected by low-level lead exposure. Hippocampal dysfunction is known to result in disruption of spatial memory. The monkeys in these experiments were tested as juveniles on a spatial memory test, the Hamilton Search Task. The monkeys exposed prenatally to lead did not show a deficit, while those exposed postnatally showed a significant deficit on the Hamilton Search Task. The deficit was not apparent until the monkeys were required to meet the most strict criterion, suggesting that the impairment may be due to the memory rather than the learning components of the task. The fact that the deficit was seen more than 3 years after the end of lead exposure indicates that the lead-induced cognitive effect is quite long-lasting and perhaps permanent.

Animals↗