Biomedical subjects

D C Rice

Publications and source records attributed to D C Rice.

At least 109 records · Page 6Linked to original sources

PubMedDate not supplied

Behavioral effects of lead in monkeys tested during infancy and adulthood.

A total of 12 monkeys (Macaca fascicularis) were dosed orally from birth with 0 or 2000 micrograms/kg/day of lead as lead acetate. Blood lead concentrations of treated monkeys peaked at an average of 115 micrograms/dl by 100 days of age and decreased to a steady state level of 33 micrograms/dl after withdrawal of infant formula at 270 days of age. At 5-6 months of age, they were tested on a nonspatial discrimination reversal paradigm. At 2.5-3.0 years of age, they were tested on a series of nonspatial discrimination reversal problems, including irrelevant cues. As adults, performance was assessed on a differential reinforcement of low rate (DRL) schedule of reinforcement, a spatial delayed alternation task, and during training on a visual discrimination task for a visual psychophysics experiment. There were no or marginal deficits on the discrimination reversal task during infancy. Although lead-treated monkeys were impaired on this task as juveniles, they were less impaired than would have been predicted based on their history of blood lead concentrations. Treated monkeys exhibited decreased interresponse times and a greater ratio of responses per reinforcement on the DRL schedule compared to controls. Four of five treated monkeys were unable to learn the visual discrimination task without a remedial training procedure in which the relevant visual stimuli were arranged to appear as if they were on the response buttons. Treated monkeys were unimpaired on the delayed spatial alternation task. The results are interpreted as suggestive of an interaction between the behavioral history of the monkeys as infants with the results of later behavioral testing.

Animals↗

PubMedDate not supplied

Fixed interval/fixed ratio performance in adult monkeys exposed in utero to methylmercury.

Previous studies in monkeys and rodents have shown the fixed interval/fixed ratio (FI/FR) schedule to be a sensitive indicator of neurotoxicity. In the present study, monkeys (Macaca fascicularis) were exposed in utero to methylmercury (MeHg). Maternal doses of MeHg of 50, 70, or 90 micrograms/kg b.wt./day resulted in infant blood mercury levels at birth ranging from 1.04 to 2.45 ppm. Monkeys were tested on a multiple FI/FR schedule of reinforcement at 8-10 years of age. Four FI/FR cycles were run per session. Pause time and run rate were calculated for FI and FR components, as well as FI quarter-life and local FI response rates. MeHg treatment and sex effects were investigated by fitting a linear orthogonal polynomial regression to each monkey's profile across sessions and performing two-way ANOVAs on the resulting linear and intercept terms. There were no treatment-related effects on either the FI or FR component for pause time or run rate. Analysis of the quarter-life revealed a significant treatment by sex effect as well as a main effect for sex. Post hoc t-tests revealed a significant difference in quarter-life of treated male and female monkeys and a marginal difference between treated and control males. The FI run rate of the male monkeys was significantly greater than that of the female monkeys whereas the FR run rate of the males was marginally greater. These results indicate that there may be a differential effect of MeHg on male and female monkeys, which could be interpreted as an effect on temporal discrimination. Overall, adult monkeys exposed to in utero MeHg exhibited a very limited sex-related effects on the FI/FR intermittent schedule of reinforcement.

Analysis of Variance↗

PubMedDate not supplied

Behavioral and electrophysiological estimates of visual thresholds in awake rats treated with 3,3',4,4',5-pentachlorobiphenyl (PCB 126).

Visual thresholds for luminance increments were obtained behaviorally and electrophysiologically from rats exposed to a polychlorinated biphenyl (PCB) during development. Male Long-Evans rats exposed to 0, 0.25, or 1.0 microg/kg/day of 3,3',4,4', 5-pentachlorobiphenyl (PCB 126) through gestation and weaning were trained as adults to perform a signal detection task. Estimates of threshold were derived from psychometric functions for each animal relating the proportion of hits to signal intensity. Thresholds derived under three luminance conditions did not differ significantly among the PCB-treated groups. After behavioral testing was completed, flash-evoked potentials were recorded from dark-adapted awake animals. Peak amplitudes increased linearly over approximately 3 log units of intensity. Extrapolations to 0 amplitude along the linear portion of the amplitude-log intensity functions produced estimates of absolute threshold of -5.44 to -5.53 log cd/m(2)-s. Waveforms recorded from awake animals had a large late negative component that was absent in previously reported anesthetized preparations. Developmental exposure to PCB 126 had no significant effect on absolute threshold or peak amplitudes and latencies.

Animals↗

PubMedDate not supplied

PCBs and behavioral impairment: are there lessons we can learn from lead?

Explore the source record for details and available documents.

Body Burden↗

PubMedDate not supplied

Lack of effect of methylmercury exposure from birth to adulthood on information processing speed in the monkey.

Although it is established that developmental methylmercury exposure produces severe motor and sensory impairment, the effect on cognitive function is less clear. To explore this issue, monkeys with robust methylmercury-induced deficits in visual, auditory, and somatosensory function were tested on a series of tasks assessing central processing speed, which is highly correlated with intelligence in humans. Five monkeys (Macaca fascicularis) were dosed from birth to 7 years of age with 50 micrograms/kg/day of mercury as methylmercuric chloride. Blood mercury levels were stable at 0.8-1.1 micrograms/g until cessation of dosing. When they were 20 years old, these monkeys and four age- and rearing-matched controls were tested on a series of simple and complex reaction time tasks. The monkey sat in a primate chair with a stainless steel bar centered at waist height. Four push buttons equidistant from the steel bar were mounted on a vertical Plexiglas panel in front of the monkey. The monkey was required to make contact with the bar, then release the bar and push the appropriate button in response to a change in stimulus conditions. For the first task (simple reaction time), the monkey was required to respond on a button when it changed from unlit to red. The monkey then performed a sequence of complex reaction time tasks: two-button, four-button, and several tasks of increasing complexity using four buttons and multiple colors. For each task, the latency to release the bar after the stimulus change (central processing speed) and to move the hand from the bar to the button (motor speed) were determined. Lastly, the monkey was required to make the quickest possible motor response on the simple reaction time task. There were no differences between groups on any aspect of the experiment. These data provide further evidence for absence of cognitive impairment in monkeys exposed developmentally to methylmercury.

Animals↗

PubMedDate not supplied

Effects of postnatal exposure of monkeys to a PCB mixture on spatial discrimination reversal and DRL performance.

Behavioral impairment as a consequence of PCB exposure beginning in utero has been reported in both humans and animals. The present study assessed the behavioral consequences of postnatal exposure to PCBs. Male monkeys (Macaca fascicularis) were dosed from birth to 20 weeks of age with 7.5 microg/kg/ day of a PCB mixture representative of the PCBs typically found in human breast milk (eight monkeys) or vehicle (four monkeys). Blood PCB levels at 20 weeks of age were 0.30-0.37 ppb for control and 1.84-2.84 ppb for treated monkeys, and fat levels were 50-198 and 1694-3560 ppb for the two groups, respectively. At about 4.5-5.0 years of age, monkeys performed on a series of three spatial discrimination reversal tasks, followed by a differential reinforcement of low rate (DRL) 30-s schedule of reinforcement. There were no differences between groups for the number of errors across reversals for any of the discrimination reversal tasks, whereas the PCB-treated group tended to have shorter median response latencies than the control group. On the DRL schedule, there were robust differences in performance between the treated and control groups. Treated monkeys displayed shorter mean and median interresponse times (IRTs), obtained fewer reinforcements, and emitted more nonreinforced responses. The treated groups also had more short IRTs (< or =10 s) than control monkeys. Performance of the treated group did not improve to control levels over the 51 sessions of the DRL 30-s schedule; their performance remained much less efficient than that of controls. The results of this study extend previous research in this cohort of monkeys, and provide further evidence that PCB exposure limited to the early postnatal period and resulting in environmentally relevant body burdens produces long-term behavioral effects.

Analysis of Variance↗

PubMedDate not supplied

Effect of postnatal exposure to a PCB mixture in monkeys on multiple fixed interval-fixed ratio performance.

Behavioral impairment as a consequence of PCB exposure beginning in utero has been reported in both humans and animals. The present study assessed the behavioral consequences of postnatal exposure to PCBs. Male monkeys (Macaca fascicularis) were dosed from birth to 20 weeks of age with 7.5 microgram(s)/kg/day of a PCB mixture representative of the PCBs typically found in human breast milk (eight monkeys) or vehicle (four monkeys). At 4 years of age, performance under a multiple fixed interval (FI)-fixed ratio (FR) schedule of reinforcement was assessed. The FI component was more sensitive to disruption as a result of PCB exposure than was the FR component. PCB-exposed monkeys displayed shorter mean interresponse times (IRTs) than controls, particularly during the earlier sessions of the experiment. Similarly, the increase in pause time characteristic of the acquisition of typical FI performance emerged more slowly across sessions in the PCB-treated group. However, the number of short IRTs (less than 5 s) remained greater in the treated group compared to controls over the 48-session duration of the experiment. On the FR component, control monkeys decreases the mean pause time across sessions whereas the PCB-treated group did not; there were no differences between groups for absolute value of average IRT or pause time. The results of this study extend previous research in this cohort of monkeys, and provide further evidence that PCB exposure limited to the early postnatal period and resulting in environmentally relevant body burdens produces long-term behavioral effects.

Adipose Tissue↗

PubMedDate not supplied

Lack of effect of 3,3'4,4',5-pentachlorobiphenyl (PCB 126) throughout gestation and lactation on multiple fixed interval-fixed ratio and DRL performance in rats.

Animals↗

PubMedDate not supplied

Effect of exposure to 3,3',4,4',5-pentachlorobiphenyl (PCB 126) throughout gestation and lactation on development and spatial delayed alternation performance in rats.

There is evidence that polychlorinated biphenyl (PCB) congeners have differential effects on endpoints of neurotoxicity depending on their chemical structure: specifically, that ortho-substituted congeners are neurotoxic whereas coplanar (dioxin-like) congeners are relatively inactive in producing neurotoxic effects. The effects of the coplanar congener 3,3',4,4',5-pentachlorobiphenyl (PCB 126) on developmental endpoints, hematology, serum biochemistry, and performance on a spatial delayed alternation task were assessed in Long-Evans rats. Dams were dosed with 0, 0.25, or 1.0 microg/kg/day Monday to Friday beginning 5 weeks before and continuing through gestation and lactation. The first 2-week breeding period produced 10, 8, and 13 litters in the three dose groups, respectively. Breeding females from the control and low-dose group that did not conceive were rebred after 76 days of dosing, producing 7 and 6 litters, respectively. Reduction in weight gain from birth to weaning at 21 days of age (DOA) was observed in both dose groups of Cohort 1 but not in Cohort 2. Males in Cohort 1 exhibited a slight decrease in anogenital distance normalized for weight. Changes in hematological and some serum biochemical parameters were observed in the pups at DOA 21 and/or 60. PCB 126 was detected in fat sampled at both DOA 21 and 60. PCB 126 was not detected in brain samples at 60 DOA in any group; analysis of Cohort 2 at DOA 21 revealed levels in the treated group about 1/100 of those in fat. On the spatial delayed alternation task, there was no convincing evidence for impairment as a result of PCB exposure, as assessed by overall accuracy of performance and measures of perseverative and other types of inappropriate responding. These data provide further evidence for the lack of neurotoxicity of dioxin-like PCB congeners. However, assessment of performance on additional behavioral indices is required before definitive conclusions may be drawn.

Animals↗

PubMedDate not supplied

Effects of postnatal exposure of monkeys to a PCB mixture on concurrent random interval-random interval and progressive ratio performance.

Behavioral impairment as a consequence of PCB exposure beginning in utero has been reported in both humans and animals. The present study assessed the behavioral consequences of postnatal exposure to PCBs. Male monkeys (Macaca fascicularis) were dosed from birth to 20 weeks of age with 7.5 microg/kg/day of a PCB mixture representative of the PCBs typically found in human breast milk (eight monkeys) or vehicle (four monkeys). Blood PCB levels at 20 weeks of age were 0.30-0.37 ppb for control and 1.84-2.84 ppb for treated monkeys, and fat levels were 50-198 and 1694-3560 ppb for the two groups, respectively. Beginning at about 5.0 years of age, monkeys performed under concurrent schedules of reinforcement in which separate random intervals were in effect on two buttons independently. After steady-state performance was reached, the relative reinforcement ratio on the buttons was changed a total of four times, and performance both during transition and steady state was examined. There was no evidence for treatment-related differences in performance across the series of changes in schedule contingencies. The negative results failed to support the hypothesis that performance on an intermittent schedule, combined with the requirement for shifting response strategy, would prove particularly sensitive to postnatal PCB exposure. Following the concurrent schedules, monkeys were tested under a progressive ratio (PR) schedule preceded by a training procedure consisting of a within-session series of increasing fixed ratios. PCB-treated monkeys emitted more responses than controls over the first few sessions of the PR, which may be indicative of retarded acquisition of their steady-state PR performance. These results extend previous studies in these monkeys on the characterization of PCB-induced behavioral deficits.

Adipose Tissue↗

PubMedDate not supplied

Low-frequency hearing loss following perinatal exposure to 3,3',4,4',5-pentachlorobiphenyl (PCB 126) in rats.

Previous research has demonstrated the sensitivity of the developing rat to the ototoxic effects of exposure to Aroclor 1254. In this study we assessed the effects of developmental exposure to an individual PCB congener (3,3',4,4',5-pentachlorobiphenyl; PCB 126) on auditory function. Nulliparous Long Evans rats received either 0, 0.25, or 1.0 microg/kg/day (5 days/week) for 35 days prior to breeding and throughout gestation and lactation. Auditory thresholds for 0.5-, 1-, 4-, 8-, 16-, 32-, and 40-kHz tones were assessed in offspring on postnatal days (PND) 76-90. Perinatal maternal PCB 126 exposure caused low-frequency hearing deficits. Elevated auditory thresholds occurred in the 1.0 microg/kg/day treated group for 0.5- and 1-kHz tones, whereas thresholds were not significantly affected at any higher frequencies. These results are important in that the data implicate, at least partially, the coplanar PCBs in the developmental ototoxicity induced by Aroclor 1254.

Aging↗

PubMedDate not supplied

Behavioral assessments of learning and attention in rats exposed perinatally to 3,3',4,4',5-pentachlorobiphenyl (PCB 126)

Evidence from humans suggests that cognitive dysfunction may result from perinatal exposure to polychlorinated biphenyls (PCBs), and the results of some animal research with PCBs have been interpreted in terms of possible impairment of attention. Long-Evans rats were fed 3,3',4,4',5-pentachlorobiphenyl (PCB 126), a coplanar congener, at doses of 0.25 or 1 microgram/kg/day [corrected] throughout gestation and nursing. Male offspring of these rats were trained as adults to perform 2 tests of attention for food reward. First, a cued target-detection task, modeled after Posner's covert orienting method for humans, was used to assess visuospatial attention. In this task, a visual target stimulus was presented in 1 visual hemifield on each trial, preceded either by a valid cue, an invalid cue, or no cue. A valid cue appeared in the same hemifield as the target, and an invalid cue appeared in the opposite hemifield. As expected, valid cues increased accuracy and speed of target detection and invalid cues decreased accuracy and speed; moreover, these effects were systematically related to changes in cue intensity and target duration. However, perinatal exposure to PCB 126 did not affect acquisition or performance of this task. The second task assessed sustained attention by means of a signal detection method in which a brief, spatially-constant but temporally unpredictable, visual signal indicated which of 2 responses would yield food. Varying the intensity of the signal greatly affected the probability of correctly reporting the signal. Perinatal exposure to PCB 126 did not affect acquisition of the response rule or performance of the task. Finally, all rats were challenged with chlordiazepoxide (CDP) at doses of 0, 3, 5, 8, or 12 mg/kg SC, 20 min before testing in the sustained attention task. In control rats, low doses (3, 5, and 8 mg/kg) of CDP reduced accuracy at low signal intensities only, suggesting an increase in visual threshold. The high dose of CDP reduced accuracy at all signal intensities and increased the false-alarm rate as well, suggesting an impairment of attention. The rats exposed perinatally to PCB 126 at 0.25 micrograms/kg [corrected] were unaffected by CDP, and those exposed to PCB 126 at 1 microgram/kg [corrected] showed a smaller decrement in performance after CDP than did the controls. Taken together, these data provide little support for the possibility that perinatal exposure to PCB 126 causes deficits in attention, but suggest that PCB 126 may alter GABA-mediated pathways in the CNS during development.

Animals↗

PubMedDate not supplied

Effects of exposure to 3,3',4,4',5-pentachlorobiphenyl (PCB 126) throughout gestation and lactation on behavior (concurrent random interval-random interval and progressive ratio performance) in rats.

There is evidence that polychlorinated biphenyl (PCB) congeners have differential effects on endpoints of neurotoxicity depending on their chemical structure: specifically, that ortho-substituted congeners are neurotoxic while coplanar (dioxin-like) congeners are relatively inactive in producing neurotoxic effects. This study extends research on the effects of developmental exposure to the coplanar congener 3,3',4,4',5-pentachlorobiphenyl (PCB 126) in Long-Evans rats. Dams were dosed with 0, 0.25, or 1 microg/kg/day Monday to Friday beginning 5 weeks before and continuing through gestation and lactation. The first 2-week breeding period produced 10, 7, and 13 litters in the three dose groups, respectively, used in behavioral assessment. Breeding females from the control and low-dose group that did not conceive were rebred after 76 days of dosing, producing six and six litters used in behavioral testing. This regimen of PCB exposure produced reduced weight gain between birth and weaning in cohort 1, and decreased thyroxine levels and changes in hematology and serum biochemistry parameters in both cohorts. One female and male from each litter were tested under a series of three concurrent random interval-random interval (RI-RI) schedules of reinforcement beginning at about 400 days of age, followed immediately by assessment under a progressive ratio (PR) schedule. The concurrent RI-RI allows assessment of performance during steady state and during behavior in transition (learning). The PR schedule provides the opportunity to assess the strength of the reinforcing event independent of response rate. During the first RI-RI schedule, the high-dose group apportioned responses less accurately than controls with respect to the scheduled relative reinforcement density on the two levers. There was also some evidence for differences in performance between treated and control groups on the third RI-RI schedule of reinforcement. There was no evidence for differences in the relative strength of the reinforcing event as assessed by PR performance. These same rats failed to exhibit PCB-induced impairment on a spatial delayed alternation task or under multiple fixed interval-fixed ratio or DRL schedules of reinforcement, performed prior to the current experiments. These data extend previous findings concerning the pattern of behavioral effects as a consequence of gestational and lactational exposure to a dioxin-like PCB congener.

Animals↗

PubMedDate not supplied

Sperm chromatin structure is altered in cynomolgus monkeys with environmentally relevant blood lead levels.

Exposure to lead has been associated with a variety of adverse reproductive outcomes such as spontaneous abortion, impaired fecundity, and sterility. Although decreased sperm counts and serum testosterone levels have been found in men with occupational lead exposure, animal experiments suggest that fertility may be impaired at blood lead levels that have no apparent effect on reproductive hormone levels or sperm concentration. Consequently, this study investigated the effect of chronic lead treatment on semen quality in healthy cynomolgus monkeys aged 15-20 years with mean (+/-SD) blood lead levels of 10 +/- 3 micrograms/dL (range 6-20 micrograms/dL, n = 4) and 56 +/- 49 micrograms/dL (range 22-148 micrograms/dL, n = 7) compared to a reference group with blood lead levels < 1.0 microgram/dL (n = 8). Blood and semen samples were collected once from each monkey in five different months. Serum testosterone levels were determined by radioimmunoassay, and lead effects on chromatin structure were analyzed by flow cytometry. There were no effects of treatment on circulating levels of testosterone or parameters of semen quality such as sperm count, viability, motility, and morphology. However, significant (p < 0.03) treatment-related effects were seen on SD alpha t values in the treated vs control animals. Group comparisons also revealed that the effects of chronic lead exposure were significant (p < 0.05) for both lead-exposed groups compared to the reference group. We conclude that chronic lead exposure alters sperm chromatin structure at blood lead levels relevant to the human population and in the absence of effects on endocrine function and traditional measures of semen quality.

Animals↗

PubMedDate not supplied

Chronic lead exposure effects in the cynomolgus monkey (Macaca fascicularis) testis.

Although reproductive consequences of high circulating blood lead levels (> or = 60 micrograms/dL) have been reported, potential adverse effects of chronic lead exposure in males that result in low to moderate blood lead levels (10-25 and 26-60 micrograms/dL, respectively) are unknown. Effects of chronic lead exposure to testis ultrastructure were determined in the cynomolgus monkey after oral administration of lead acetate (1500 micrograms/kg BW/day) in a vehicle in the following groups: from birth to 10 years (lifetime), postnatal day 300 to 10 years (postinfancy), and postnatal day 0-400 (infancy); monkeys in the control group received only the vehicle (95% glycerol and 5% distilled water). At age 10 years, circulating lead concentrations in lifetime and postinfancy-dosed monkeys were approximately 35 micrograms/dL, and in control and infancy animals the concentrations were < 1.0 microgram/dL. Sertoli and spermatogenic cells of dosed monkeys from the infancy and lifetime groups revealed injuries. Chronic exposure to lead that results in moderate blood lead concentrations induced persistent ultrastructural alterations in the cynomolgus monkey testis. Results of this study on the primate, following extrapolation to humans, could influence further refining of the impact of environmental lead contamination concentrations vis-à-vis the health of children, adults, and aged human beings.

Animals↗

PubMedDate not supplied

Neonatal low-level lead exposure in monkeys (Macaca fascicularis): effect on two-choice non-spatial form discrimination.

Monkeys were dosed orally with 500 microgram/kg/day of lead as lead acetate from day 1 of life. No overt signs of lead toxicity were observed. At 2--3 years of age they were tested on a two-choice non-spatial form discrimination using a WGTA apparatus. Treated monkeys showed deficits compared to controls on a series of 20 discrimination reversals; there was no difference between the groups in the effect of a series of "overtraining" trials introduced between reversals.

Animals↗

PubMedDate not supplied

Lead-induced changes in learning: evidence for behavioral mechanisms from experimental animal studies.

Lead is probably the most studied of the neurotoxic agents, both in humans and in animal models. Research has focused on learning impairment and other behavioral consequences produced by developmental exposure. In children, lead exposure results in deficits in such global measures as IQ, as well as more specific deficits that are suggestive of attentional deficit disorder. Research in animals has also clearly demonstrated learning and memory deficits as a consequence of developmental lead exposure. Experiments performed in monkeys implicate the same behavioral problems as those observed in children: increased distractibility, inability to inhibit inappropriate responding, and perseveration in behaviors that are no longer appropriate. For example, lead-treated monkeys were impaired in their ability to perform discrimination reversal task, but not on the initial visual discrimination task. Deficits were more severe in the presence of distracting irrelevant stimuli. Lead-treated monkeys displayed severe perseveration on one button on a task which required them to alternate responding between two buttons. Lead-treated monkeys displayed memory impairment on a task requiring them to remember a previously observed stimulus or position, which was at least in part the result of interference from responses from previous trials. Lead-treated monkeys exhibited a higher rate of response on an intermittent schedule of reinforcement, and had difficulty inhibiting responding when required. Thus, for many of the tasks on which monkeys have been found to display learning and/or memory impairment, the deficit can be attributed at least in part to an attentional deficit and/or perseverative behavior.

Animals↗

PubMedDate not supplied

Evidence for delayed neurotoxicity produced by methylmercury.

Delayed toxicity as a result of developmental methylmercury exposure was identified in mice two decades ago by Spyker, who observed kyphosis, neuromuscular deficits, and other severe abnormalities as the mice aged. Delayed neurotoxicity was also observed in monkeys treated with methylmercury from birth to seven years of age. When these monkeys reached 13 years of age, individuals began exhibiting clumsiness not present previously. Further exploration revealed that treated monkeys required more time to retrieve treats than did nonexposed monkeys and displayed abnormalities on a clinical assessment of sense of touch in hands and feet, despite the fact that clinical examinations performed routinely during the period of dosing had not yielded abnormal results. Another group of monkeys, dosed from in utero to four years of age, also took longer to retrieve treats when assessed years after cessation of exposure. These observations were pursued in both groups of monkeys by objective assessment of somatosensory function in the hands: both groups of monkeys exhibited impaired vibration sensitivity. These results are strongly suggestive of a delayed neurotoxicity manifested when these monkeys reached middle age. Data from persons with Minamata disease also provide evidence for delayed neurotoxicity. Perhaps the strongest piece of evidence comes from a study of over 1100 Minamata patients over 40 years old, in which difficulty in performing daily activities increased as a function of age compared to matched controls. Methylmercury may represent the only environmental toxicant for which there is good evidence for delayed neurotoxicity that may be manifested many years after cessation of exposure.

Animals↗