Problems in replacing a consultant.
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Attitude↗
Biomedical subjects
S E Robinson
Publications and source records attributed to S E Robinson.
Challenges of recording human fetal auditory-evoked response using magnetoencephalography.
OBJECTIVE: Our goals were to successfully perform fetal auditory-evoked responses using the magnetoencephalography technique, understand its problems and limitations, and propose instrument design modifications to improve the signal quality and success rate. METHODS: Fetal auditory-evoked responses were recorded from four fetuses with gestational ages ranging from 33-40+ weeks. The signals were recorded using a gantry-based superconducting quantum interference device. Auditory stimulus was 1 kHz tone burst. The evoked signals were digitized and averaged over an 800 ms window. RESULTS: After several trials of positioning and repositioning the subjects, we were able to record auditory-evoked responses in three out of the four fetuses. Since the superconducting quantum interference device array design was not shaped to fit over the mother's abdomen, we experienced difficulty in positioning the sensors over the fetal head. CONCLUSIONS: Based on this pilot study, we propose instrument design that may improve signal quality and success rate of the fetal magnetic auditory-evoked response.
Equipment Design↗
Effect of prenatal opioid exposure on cholinergic development.
Opioid drugs such as methadone or buprenorphine are often used in the management of pregnant addicts. These drugs are generally thought of as nonteratogenic and preferable to repeated cycles of withdrawal in utero. However, evidence exists that perinatal exposure to these opioids delays and disrupts cholinergic development, particularly in the striatum. Acetylcholine (ACh) content and the expression of choline acetyltransferase protein and mRNA are reduced in the early postnatal period by prenatal opioid exposure in the rat. Although these indicators of the cholinergic phenotype return to normal levels over time, the activity of the cholinergic neurons remains disrupted, with a large increase in ACh turnover rate. The mechanism of these effects is unknown, but may involve changes in the expression of nerve growth factor, which is reduced by opioid exposure.
Acetylcholine↗
Neonatal administration of delta-9-tetrahydrocannabinol (THC) alters the neurochemical response to stress in the adult Fischer-344 rat.
Fischer-344 rat pups were injected with either 10 mg/kg delta 9-tetrahydrocannabinol (THC) or vehicle on postnatal days 4,6 and 8. Pups were then allowed to mature. On day 129 of age rats were exposed to a stress paradigm which consisted of inescapable electric foot-shock administered at 1 mA for 15 sec daily for 8 days. Analgesia induced by foot-shock was measured by tail withdrawal from 55 degree C water. On the 9th day rats were exposed to the shock environment only. Fifteen minutes following measurement of tail withdrawal, animals were sacrificed. Plasma corticosterone and prolactin were measured. Levels of norepinephrine, dopamine and 5-hydroxytryptamine and metabolites were determined in frontal cortex, hippocampus and hypothalamus. Neonatal exposure to THC produced an increase in baseline tail withdrawal latency. No effect of THC exposure was seen on acute stress-induced analgesia. Rats exposed to THC required a greater number of conditioning trials to develop conditioned analgesia than animals treated neonatally with vehicle. The conditioned stress increased plasma corticosterone without affecting prolactin. Stress increased hypothalamic 5HT and 5HIAA while decreasing 5HT turnover in this area. Dopamine and DOPAC levels in the hypothalamus and frontal cortex were increased by stress; dopamine turnover in the frontal cortex was elevated by stress. Neonatal THC and stress elevated norepinephrine above control levels in the hypothalamus, while increasing 5HT in the hippocampus and frontal cortex. The stress-induced increase in DOPAC in the frontal cortex was decreased by THC exposure. These data suggest that long-term neurochemical changes may occur with neonatal administration of THC.(ABSTRACT TRUNCATED AT 250 WORDS)
3,4-Dihydroxyphenylacetic Acid↗
The effect of prenatal methadone exposure on development and nociception during the early postnatal period of the rat.
The effects of prenatal exposure to methadone via Alzet osmotic minipump on early postnatal development and on nociceptive behavioral endpoints were assessed in Sprague-Dawley rat pups during the first three postnatal weeks. This treatment regimen appeared to produce no maternal toxicity, with dams developing and maintaining dependence upon methadone through parturition. Methadone-exposed dams exhibited a withdrawal syndrome consisting of wet-dog shakes, diarrhea, vocalizations and irritability when challenged with naloxone 24 h postpartum. Pups exhibited a similar withdrawal syndrome following naloxone challenge consisting of mouthing and licking, hyperactive response to touch and vocalizations 24 h postpartum. Although no significant difference in litter size was evident in methadone-treated litters, a 16% pup mortality rate was observed in these litters. Prenatal methadone-exposed pups exhibited a significant body weight reduction at birth that resolved by postnatal day 2 (P2) in males and P4 in females. Methadone-exposed pups exhibited significant developmental delay in the expression of the negative geotaxic response to a morphine challenge while, conversely, 21-day-old pups exhibited a significantly reduced analgesic response to this challenge. These studies indicate that this method of prenatal exposure to methadone can produce dependence in the dam and offspring without substantial mortality, induce developmental delay and alter analgesic responses to opiate challenge in exposed pups during the preweanling period.
Animals↗
Intravenous gestational cocaine in rats: effects on offspring development and weanling behavior.
Pregnant rats were injected with cocaine (CN; 6 mg/kg) or an equal volume of saline (SAL), via the tail vein, on gestation days 8-20. A third group was untreated (UT). Maternal weight gain was not affected by dam treatment despite slight differences in food intake. Litter characteristics (e.g., litter size, pup weight) did not differ among groups. Indices of fetal mortality were not affected by the treatments. Developmental tests, initiated on postnatal day (PND) 2, indicated slight delays in the negative geotaxic response and eye opening in cocaine-exposed pups. Open-field and tail-flick tests were performed on PND 21. Pups were acutely injected with cocaine (10 mg/kg, IP), saline, or received no treatment before placement in a novel open field; morphine (1.5 mg/kg, SC) or saline was injected prior to the tail flick test. Pups from CN dams exhibited a significant decrease in spontaneous exploratory behavior compared to both controls, and a time-dependent increase in rearing compared to pups from UT dams. The acute cocaine injection prior to placement in the open field did not alter locomotion or rearing among dam treatment groups. However, the acute cocaine injection did increase stereotypy ratings for female pups from CN dams compared to similarly treated males, and females from SAL and UT dams. No differences were observed among groups in the tail-flick test. These data suggest that the IV route of administration provides a viable method of cocaine delivery in pregnant rats, and provides further evidence of the developmental and behavioral teratogenicity of prenatal cocaine exposure.
Animals↗
Perinatal methadone exposure affects dopamine, norepinephrine, and serotonin in the weanling rat.
On gestational day 7 pregnant rats were implanted with osmotic minipumps containing either methadone hydrochloride (initial dose, 9 mg/kg/day) or sterile water. Their offspring were cross-fostered so that they were exposed to methadone prenatally and/or postnatally. On postnatal day 21, dopamine (DA), norepinephrine (NE), serotonin (5-HT), and their metabolites were analyzed. Perinatal methadone exposure disrupted dopaminergic, noradrenergic, and serotonergic activity in a brain region- and gender-specific fashion. The ratio of the DA metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) to DA was reduced in the frontal cortex of males exposed to methadone postnatally. No effects of perinatal methadone exposure were observed on DA and DOPAC in the striatum. The ratio of 3-methoxy-4-hydroxyphenylglycol (MOPEG) to NE in the hippocampus was increased significantly in males exposed to methadone prenatally. Striatal and parietal cortical 5-hydroxyindoleacetic acid (5-HIAA), but not its ratio to 5-HT, was increased slightly in rats exposed to methadone postnatally. Although parietal cortical 5-HT, 5-HIAA, and 5-hydroxytryptophan were all affected by perinatal methadone exposure, the ratios of metabolite and precursor to 5-HT were not affected. Effects of methadone exposure appeared to depend upon the developmental stage at which exposure occurred and did not appear to result from the phenomenon of neonatal withdrawal. Changes in activity of these three neurotransmitter systems may contribute to the effect of perinatal methadone on the activity of other neurons, such as cholinergic neurons.
Animals↗
Prenatal nicotine sex-dependently alters agonist-induced locomotion and stereotypy.
This study examined the effects of prenatal nicotine exposure (2 mg/kg/day) via s.c. osmotic minipumps, gestational days 7-22, on nicotine- and lobeline-induced locomotor activity and stereotypy in 14-day-old rat pups. Prenatal nicotine exposure increased fetal mortality and produced decreases in weight gain apparent after weaning, but did not affect acquisition of developmental milestones. Compared to male pups prenatally exposed to saline, those prenatally exposed to nicotine and challenged with nicotine (1 mg/kg, i.p.) exhibited significantly greater locomotor activity, whereas a lobeline challenge (1 mg/kg, s.c.) produced significantly greater stereotypy. No effects of prenatal exposure were observed on locomotor activity or stereotypy in females. Results suggest that 1) central control of motor function may be more vulnerable to prenatal nicotine in males, and 2) nicotine and lobeline possess distinct pharmacological profiles.
Animals↗
Developmental effects of intermittent prenatal exposure to 1,1,1-trichloroethane in the rat.
The effects of daily three 1-h exposures to 7000 ppm 1,1,1-trichloroethane (TCE) on physical and behavioral development were examined in Sprague-Dawley rats exposed during the last week of gestation. A sham group was exposed to filtered air. Offspring of both groups were fostered to untreated dams. No significant group differences were detected in total maternal weight gain or food and water consumption, but differences were observed in initial litter characteristics, including a longer gestation period in the TCE group, a smaller number of litters delivered in the TCE group, and fewer live pups per litter in the TCE group. At birth, the total litter weight was less in the TCE group, but there was no significant difference in average pup weight. Pups prenatally exposed to TCE did not differ from shams in day of eye opening, pinnae detachment, or incisor eruption. The TCE group weighed less the first 2 weeks of life, was impaired in its ability to perform the inverted screen, negative geotaxis, and vertical screen tests, and had less forelimb grip strength. Locomotor activity was reduced in the TCE group, and the ratio of brain to body weight was reduced in TCE-exposed offspring. These data provide evidence for neurobehavioral teratogenicity of intermittent prenatal exposure to high concentrations of TCE in rats.
Animals↗
Attendance at a breast screening clinic: a problem of administration or attitudes.
In a study of why a sample of women, aged 45-64 and registered with a group practice in Edinburgh, attended or did not attend the Edinburgh Breast Screening Clinic demographic, aetiological, social, and perceptual characteristics of attenders and non-attenders were compared. Similar proportions of attenders and non-attenders knew the chance of a breast lump being cancer and were aware of the benefits of early diagnosis and treatment. The study, however, suggests that non-attenders saw the screening clinic as a place of risk while the attenders saw screening in a positive light: 79% of non-attenders as compared with 36% of attenders said that they were afraid of cancer being found, and most women attended either to reassure themselves that they had not got breast cancer or to receive early treatment if they had. Furthermore, 72% of non-attenders as compared with 13% of attenders were anxious that their lives would be disrupted if cancer were found at the screening clinic. There may well be an important irreducible element to non-attendance due to attitudinal factors; the ethical implications of attempting to eliminate this require careful consideration.
Attitude to Health↗
Effects of postweaning administration of delta-9-tetrahydrocannabinol (THC) on adult behavioral and neuroendocrine function in Sprague-Dawley and Fischer-344 rats.
Delta-9-tetrahydrocannabinol (THC) was administered to young male Fischer-344 (CDF) and Sprague-Dawley (CD) rats on days 30-50 of age. Doses of THC consisted of 20, 10 or 5 doses of 10 mg/kg spaced over the 20-day period. On day 140 animals were exposed to a 15 sec 1.5 mA scrambled foot-shock. Latency for withdrawal from 55 degrees C water was used as a measure for analgesia. Both CDF and CD rats showed a foot-shock induced analgesia (FSIA). Animals which had received 5 or 10 doses of THC in youth showed an enhanced response to foot-shock in the CDF rat. The foot-shock was then paired with an unconditioned stimulus (shock environment) and a conditioned analgesia developed over 4 days. At weekly intervals thereafter animals were tested in the shock environment only for extinction of the analgesic response. Over 4 weeks, analgesia did not show extinction in the CDF rat. Extinction of the response was observed in the veh and 20 dose groups in the CD rat; whereas a resistance to extinction was observed in the other groups. The CDF rats were then sacrificed following the last extinction trial and serum corticosterone and prolactin measured. Five and 10 doses of THC decreased prolactin levels; stress, however, increased these levels above the levels in VEH treated animals exposed to stress. Extinction of a fixed ratio 10 as well as exposure to fixed ratio strain in the CD rat were not affected by THC. These data suggest that THC administered during postweaning development alters endogenous systems which mediate the animals response to stress.
Age Factors↗