PubMed Health⌕ Search

Biomedical subjects

R E Bowman

Publications and source records attributed to R E Bowman.

At least 19 recordsLinked to original sources
PubMed2005

Stress-induced changes in spatial memory are sexually differentiated and vary across the lifespan.

Stress exposure, depending on intensity and duration, elicits adaptive or maladaptive physiological changes. The same general pattern of advantageous versus deleterious stress effects appears to exist for some cognitive functions, particularly spatial learning and memory performance. This article reviews sex differences in response to stress on a variety of spatial tasks. In general, females are more resistant than males to stress-induced impairments on spatial tasks, including the radial arm maze and object placement. In young adulthood, chronic stress (restraint, 6 h per day for 21 days) impairs male performance on both tasks but leads to behavioural enhancements in females. Furthermore, these sex-dependent stress effects are influenced by both organisational and activational oestrogenic effects. Additionally, sex-specific stress responses vary depending on developmental age at the time of stress exposure. Male behavioural stress responses appear fixed across the lifespan (i.e. stress-induced cognitive impairments) whereas female stress responses appear more variable (i.e. stress-induced enhancements observed in young adulthood are different in response to prenatal stress and diminished following stress exposure at old age). These findings underscore the point that many effects obtained in males cannot be generalised to females and highlight the need to investigate the stress response at different ages and in both sexes.

Adaptation, Physiological↗
PubMed2002

Effects of chronic restraint stress and estradiol on open field activity, spatial memory, and monoaminergic neurotransmitters in ovariectomized rats.

Twenty-one days of chronic restraint stress impairs male rat performance on the radial arm maze [Luine et al. (1994) Brain Res. 639, 167-170], but enhances female rat performance [Bowman et al. (2001) Brain Res. 904, 279-289]. To assess possible ovarian hormone mechanisms underlying this sexually dimorphic response to stress, we examined chronic stress effects in ovariectomized rats. Ovariectomized rats received Silastic capsule implants containing cholesterol or estradiol and were assigned to a daily restraint stress (21 days, 6 h/day) or non-stress group. Following the stress period, subjects were tested for open field activity and radial arm maze performance. Stress and estradiol treatment affected open field activity. All stressed animals, with or without estradiol treatment, made fewer total outer sector crossings. In contrast, estradiol-treated animals, with or without stress, made more inner sector visits, an indication that estradiol decreased anxious behavior on the open field across time. As measured by the total number of visits required to complete the task, stress did not affect radial arm maze performance in ovariectomized rats, but estradiol-treated animals, with or without stress, performed better than non-treated animals on the radial arm maze. Stressed subjects receiving estradiol showed the best radial arm maze performance. Following killing, tissue samples were obtained from various brain regions known to contribute to learning and memory, and monoamine and metabolite levels were measured. Several changes were observed in response to both stress and estradiol. Most noteworthy, stress treatment decreased homovanillic acid levels in the prefrontal cortex, an effect not previously observed in stressed intact females. Estradiol treatment increased norepinephrine levels in CA3 region of the hippocampus, mitigating stress-dependent changes. Both stress and estradiol decreased dentate gyrus levels of 5-hydroxyindole acetic acid. In summary, the current study provides novel information showing that estradiol alters behavioral and neurochemical responses to stress in ovariectomized rats. Estradiol treatment decreased anxious behavior on the open field and stressed animals receiving estradiol had enhanced radial arm maze performance. In relation to interactions between stress and estradiol on cognition and anxiety, changes in the prefrontal cortex dopaminergic system, dentate gyrus serotonergic system, and norepinephrine levels in the CA3 region appear important. Results show that estradiol may moderate stress effects on cognition and anxiety through both organizational and activation effects.

Animals↗
PubMed2001

Chronic restraint stress enhances radial arm maze performance in female rats.

Effects of chronic restraint stress (21 and 28 days) on physiological and behavioral parameters in female rats were examined. Total (bound and free) and free corticosterone (CORT) levels were measured at different time points during the stress period. Higher total CORT levels were observed in stressed rats during the stress period but returned to baseline at 15 days post-stress. Additionally, free CORT levels decreased across the stress period. Estrous cyclicity was monitored daily in all animals. Stress had no apparent effects on estrous cyclicity, in rats with either normal length or elongated estrous cycles, but stressed females gained less weight than controls. Following the stress period, subjects were tested for open field activity and radial arm maze (RAM) performance. Females stressed for 21 days showed enhanced spatial memory performance on the RAM. A longer period of restraint, 28 days, also led to less weight gain by stressed subjects and unaltered estrous cycle lengths, but was not associated with enhanced RAM performance. Further analysis indicated that RAM performance was influenced by specific estrous cycle day, particularly during proestrus. Following 21 days of restraint stress all animals in proestrus, regardless of treatment, showed impaired acquisition. After 28 days, stressed females in proestrus performed better than proestrus controls. These results are discussed in relation to previously reported effects of stress in male rats.

Animals↗
PubMed1995

Immunoresponsiveness in endometriosis: implications of estrogenic toxicants.

Endometriosis is a reproductive disease characterized by the growth of endometrial cells at sites outside the uterus. This disease is a serious disorder associated with chronic pain and infertility, which may be present in 6 million women in this country. Traditional medical therapy has consisted of hormonal regimens that limit the action of endogenous estrogen. The etiology of endometriosis is unknown, but studies suggest that soluble factors known as cytokines play a role in disease pathogenesis. 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD or dioxin) is an environmental toxicant that alters the action of estrogen in reproductive organs and adversely affects immunocompetence. The incidence of endometriosis was determined in rhesus monkeys that were chronically exposed to dioxin for a period of approximately 4 years. Ten years after termination of dioxin treatment, the presence and severity of endometriosis was assessed by surgical laparoscopy. The incidence of endometriosis correlated with dioxin exposure and disease severity was dependent upon the dose administered. Moderate to severe endometriosis was not found in control animals but was documented in three of seven animals exposed to 5 ppt dioxin (43%) and in five of seven animals exposed to 25 ppt dioxin (71%). The frequency of spontaneous disease in the control group was 33%, similar to an overall prevalence of 30% in 304 rhesus monkeys with no history of dioxin exposure. This study indicates that endometriosis may be associated with dioxin exposure in the rhesus. In view of overwhelming evidence that cytokines participate in the mediation of reproductive-endocrine phenomena and regulation of endometrial growth, future assessment of the effects of environmental toxicants on reproductive health may depend upon our understanding of the bidirectional cytokine network between the immune and endocrine systems.

Animals↗
PubMed1993

Endometriosis in rhesus monkeys (Macaca mulatta) following chronic exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin.

The incidence of the reproductive disease endometriosis was determined in a colony of rhesus monkeys chronically exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD or dioxin) for a period of 4 years. Ten years after termination of dioxin treatment, the presence of endometriosis was documented by surgical laparoscopy and the severity of disease was assessed. The incidence of endometriosis was directly correlated with dioxin exposure and the severity of disease was dependent upon the dose administered (p < 0.001). Three of 7 animals exposed to 5 ppt dioxin (43%) and 5 of 7 animals exposed to 25 ppt dioxin (71%) had moderate to severe endometriosis. In contrast, the frequency of disease in the control group was 33%, similar to an overall prevalence of 30% in 304 rhesus monkeys housed at The Harlow Primate Center with no dioxin exposure. This 15-year study indicates that latent female reproductive abnormalities may be associated with dioxin exposure in the rhesus. Therefore, the effects of this toxin may be more diverse than previously recognized.

Animals↗
PubMed1991

Problem solving in elderly sophisticated and naive monkeys.

Elderly (greater than 23 years) rhesus monkeys, some of whom had previous learning test experience, were tested on a standardized battery of discrimination and concept-formation tasks, and their performance was compared with that of test-naive middle-aged (15 years) and juvenile (2 years) monkeys. Naive elderly monkeys performed more poorly on virtually all tasks compared to their younger counterparts. In contrast, test-experienced elderly monkeys outperformed both middle-aged and juvenile monkeys on those problem types with which they had limited previous experience, despite the fact that 8-10 years had passed since their prior training. However, test-experienced elderly monkeys did not display superior performance on new tests that approximated visual acuity or assessed delayed discrimination capabilities.

Aging↗
PubMed1990

Long-term effects of developmental halothane exposure on radial arm maze performance in rats.

Chronic exposure of rats to low levels of halothane during development, a treatment which retards synaptogenesis, was found to cause a long-term impairment of choice accuracy in the radial-arm maze. In Expt. 1, the relative importance of dose level and dosing regimen was examined. Dose level seemed the more critical variable for causing impaired choice accuracy. Exposure to 100 parts per million (ppm) of halothane in the air either on an intermittent or continuous schedule from day two of conception until 60 days after birth significantly impaired choice accuracy, whereas exposure to 25 ppm on a continuous schedule did not cause a deficit, even though with this condition the total amount of halothane exposure was about the same as with 100 ppm given intermittently. In Expt. 2, the 100 ppm intermittent exposure regimen was used to examine the relative importance of exposure during early and late developmental periods for producing the cognitive effects of halothane. Groups were divided into those exposed to halothane during gestation and until 30 days after birth (early exposure), those exposed from day 31 until day 90 (late exposure) and those exposed during both early and late periods (combined exposure). Adverse effects on choice accuracy were seen with all 3 types of exposure, but surprisingly, it was the late exposure that caused the most severe effects. These results show that developmental exposure to halothane which impairs synaptogenesis also causes long-lasting cognitive impairment. Halothane exposure can be a useful experimental tool for examining the relationship between synaptic and behavioral development.

Age Factors↗
PubMed1989

Suppressive effects of halothane on reactive synaptogenesis in the dentate gyrus of rats.

Reactive synaptogenesis was studied in the dentate gyrus of rats exposed to 100 parts per million of halothane for 15 days starting on the day after unilateral entorhinal lesioning. Halothane exposure markedly affected the replacement of synapses. Only 17% of the lost synapses were restored by day 15 postlesion in rats exposed to halothane, while 73% of the lost synapses were recovered in rats not exposed to halothane. However, this suppression in initial reactive synaptogenesis did not result in permanent deficits in synaptic population. After halothane exposure was stopped, reactive synaptogenesis resumed, and by day 30 after the lesion, the synaptic population of the experimental group caught up to the control level. This suppressive action of halothane suggests its utility as a research tool for delaying synaptogenesis during selected developmental epochs to study the relationship between synaptic and behavioral recovery.

Animals↗
PubMed1989

Effects of lead on luteal function in rhesus monkeys.

Exposure to lead in the workplace or home environment has been implicated as a cause of decreased fertility in women. In a previous study, as part of our effort to determine effects of lead in primates, female rhesus monkeys were exposed to lead acetate in drinking water (n = 10) or provided water with no added lead (n = 7) for 33 mo. Lead was administered at levels between 2 and 8 mg/kg/day, with doses adjusted to keep blood lead values near a target of 70 micrograms/dl (observed mean +/- SEM = 68.9 +/- 6.54 micrograms/dl). Blood lead concentrations in control animals were less than 10 micrograms/dl. No significant differences were detected between control and experimental animals in body weight, hematocrit, or general health. Female monkeys receiving lead exhibited longer and more variable menstrual cycles and shorter menstrual flow. In the present study, circulating amounts of progesterone (P4) were determined to evaluate luteal function during the final 7 mo of treatment with lead. Several characteristics were altered as a result of lead treatment: circulating amounts of P4 were reduced as indicated by relative units of area under the concentration-time curve, maximal amounts of P4 were reduced, and P4 levels were greater than 1 ng/ml on fewer days. There were no significant differences between groups in mean percent of anovulatory cycles. Therefore, although chronic treatment with the levels of lead used in this study did not prevent ovulation, luteal function was suppressed. These results extend previous observations of adverse effects of lead on ovarian activity and fertility in monkeys.

Animals↗
PubMed1988

Behavioral effects of developmental lead exposure in rhesus monkeys.

Postnatal lead exposure has been found to cause long-term learning and memory deficits in monkeys. Pulse-chronic exposure, consisting of acute high-level exposure followed by chronic lower-level exposure, has been particularly effective in causing these impairments. We investigated possible antecedents of lead-induced cognitive dysfunction by evaluating the behavioral effects of pulse-chronic lead exposure in rhesus monkeys during the first 6 months of postnatal life. Blood lead concentrations in the monkeys reached a peak of 55.8 +/- 7.8 ug/dl during week 5 after birth and then averaged between 33.1 and 42.9 ug/dl during the rest of the first 6 months after birth. Zinc protoporphyrin levels were increased by lead exposure, but hematocrits were unaffected. Significant lead-related effects were detected on a visual exploration test and a neonatal behavioral assessment battery. Lead-treated monkeys exhibited decreased looking behavior on the visual exploration test and decreased muscle tonus and increased arousal or agitation on the behavioral assessment battery. No effects were seen on a Piagetian object permanence task and no toxic effects on health or growth were detected. In addition to providing indices of behavioral dysfunction during postnatal lead exposure, performance on these early behavioral tests may predict later lead-induced cognitive dysfunction.

Animals↗
PubMed1988

Delayed spatial alternation deficits resulting from perinatal PCB exposure in monkeys.

Monkeys exposed to low, chronic levels of polychlorinated biphenyls (PCBs) in utero and during nursing until 4 months after birth were tested at 4-6 years of age on delayed spatial alternation (DSA), a spatial learning and memory task. Deficits in performance accuracy were detected in two cohorts of monkeys whose mothers had been fed 2.5 ppm of the PCB mixture, Aroclor 1248, in their diet for an 18-month period ending at least 12 months prior to pregnancy. The deficit was most apparent at the shorter delays, suggesting that it was not due to memory impairment, but may have been due to impairments in associational or attentional processes. There may also have been a deficit in a group of monkeys whose mothers were fed 1.0 ppm of the PCB mixture, Aroclor 1016. However, the deficit in this group was less pronounced than in the other groups. The appearance of a PCB-induced cognitive deficit more than 3 years after the end of exposure indicated the existence of very long-term adverse consequences of low-level perinatal PCB exposure.

Animals↗
PubMed1987

Effect of chronic exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin on sister chromatid exchange levels in peripheral lymphocytes of the rhesus monkey.

Frequencies of sister chromatid exchanges and chromosomal aberrations were examined in peripheral lymphocytes of Rhesus monkeys which had been fed a diet containing 25 parts per trillion 2,3,7,8-tetrachlorodibenzo-p-dioxin for a period of 4 years. When compared to non-exposed control animals, no significant differences were noted for either of these cytogenetic endpoints. In addition, there was not a significant difference in sister chromatid exchange response to a challenge dose of mitomycin C in cells from 2,3,7,8-tetrachlorodibenzo-p-dioxin exposed animals compared to controls. Our results confirm the lack of genotoxic effects associated with 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure.

Animals↗
PubMed1987

Psychopharmacological investigations of a lead-induced long-term cognitive deficit in monkeys.

This study investigated pharmacological manipulations of the cholinergic (ACh) and dopaminergic (DA) transmitter systems in monkeys with a long-term lead-induced cognitive deficit on delayed spatial alternation (DSA). Both ACh and DA have been found to be affected by developmental lead exposure and to be involved with performance on spatial learning and memory tasks. The lead-induced deficit in performance accuracy on DSA persisted throughout the 2 years of this experiment, which ended more than 8 years after the end of the postnatal lead exposure. Acute administration of agonists and antagonists of the ACh and DA systems did not elicit differential effects from the lead-exposed and control groups in terms of DSA per cent correct performance. The ACh antagonist, scopolamine, caused a dose-related decline in performance in both groups. Significant amelioration of the lead-induced DSA deficit was achieved by chronic treatment with the DA agonist, L-dopa. After withdrawal from L-dopa, the lead-related deficit reappeared. Improvement in performance of the lead-treated group was also seen after chronic amphetamine administration, but this effect was not significant. These data implicate DA mechanisms in the long-lasting cognitive effects of developmental lead exposure. The alleviation of the deficit with chronic administration of a DA precursor points to a possible line of treatment for the cognitive effects of developmental lead exposure.

Acetylcholine↗
PubMed1987

Neurobehavioral effects of chronic halothane exposure during developmental and juvenile periods in the rat.

Chronic exposure of rats to the surgical anesthetic agent halothane during development has been found to cause both neural and behavioral impairment. Among the halothane-induced deficits are retarded synaptogenesis and impaired spontaneous alternation. It is unclear how long after birth the susceptibility to the neurotoxic effects of halothane persists. The present study compared in rats the effects of halothane exposure on synaptic density and spontaneous alternation during early and late periods of maturation. All three experimental groups were exposed to 100 parts per million of halothane for 8 h/day, 5 days/week. One group (early exposure) was exposed from day 2 of conception until 30 days after birth. The second group (late exposure) was exposed to the same amounts from day 31 until day 90 after birth. The third group (continued exposure) received both periods. The control group was treated in the same way, but was not exposed to halothane. As found in the previous study, there were greater effects of halothane on synaptogenesis than on spontaneous alternation; impairment of spontaneous alternation behavior was found only with the early exposure. Deficits in synaptic density were found with both early and late exposure, although the early exposure had more severe effects. Halting the exposure to halothane on day 30 reinstated control-like rates of synaptogenesis, but the deficit in synaptic density from the early exposure persisted into adulthood. The potent neurotoxic effect of halothane in suppressing synaptogenesis highlights not only its potential as a hazard but also its potential as an experimental tool for manipulating the rate of synaptogenesis and examining the relationship between synaptic development and behavioral maturation.

Aging↗
PubMed1987

Altered menstrual cycles in rhesus monkeys induced by lead.

Adult, female rhesus monkeys ingested lead daily for three 1-year exposures over a 5-year period followed by chronic lead intake for 3 additional, consecutive years. Lead was administered as lead acetate in the drinking water at levels producing average circulating concentrations of lead between 44 and 89 micrograms/100 ml and zinc protoporphyrin concentrations between 87 and 105 micrograms/100 ml. The monkeys were without overt signs of lead toxicity at all times; i.e., appetite, body weight, and hematocrit levels were normal. Menstrual cycles were altered by lead. During the last 2 years of exposure, the lead-treated monkeys had less frequent cycles, longer and more variable intercycle intervals, and fewer days of vaginal bleeding than controls. These differences were not due to seasonal artifacts or differences in exposure to environmental influences such as light or diet. Further, historical data indicated that cycles were normal for the treated monkeys prior to exposure to lead and that three of four cycle characteristics remained normal during the first lead exposures. Duration of vaginal bleeding was initially attenuated by lead but returned to normal when lead intake was discontinued between exposures. In contrast, the effects of lead observed during the later years of exposure remained apparent 1 year following termination of lead ingestion. These results suggest that persistent alterations of the menstrual cycle and perhaps premature menopause resulted from prolonged exposure to lead at levels which produced no obvious signs or symptoms of toxicosis.

Animals↗
PubMed1986

Effects of the dopamine D-2 receptor agonist, LY 171555, on radial arm maze performance in rats.

Rats trained to run through an 8-arm radial maze for food reinforcement were injected with a broad range of doses of the dopamine D-2 receptor agonist, LY 171555. Deficits were detected by the choice measures of entries to repeat and arms entered in the first eight choices. There was a dose-related increase in latency to finish the maze even though there was no significant increase in the number of choices needed to finish the maze.

Animals↗
PubMed1986

Scopolamine effects on Hamilton search task performance in monkeys.

The Hamilton search task, a test of spatial memory, was given to adult monkeys after administration of scopolamine. Three monkeys had been exposed to lead during development and two were controls. The task consisted of opening eight boxes, one per trial, for food reinforcement, with a 20 second delay between trials. The monkey had to remember which boxes it had already opened and avoid them to obtain the remaining reinforcements. Percent correct response, openings-to-repeat, trials per session, repetitive index and response latency were measured. There were no significant lead-related effects. Significant scopolamine-induced deficits were detected with four of the measures. The low doses of scopolamine (1-3 micrograms/kg) did not affect response accuracy, but 15 and 30 micrograms/kg caused impairments. Only 30 micrograms/kg substantially increased latency. This is like other memory tests in monkeys and rats in that it is sensitive to anticholinergic challenge. Cognitive performance deficits were detected at a dose (15 micrograms/kg) which did not cause increased response latency. The Hamilton search task is a flexible and sensitive memory task for monkeys, analogous to the radial arm maze in the rat.

Animals↗