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H A Tilson

Publications and source records attributed to H A Tilson.

At least 163 records · Page 9Linked to original sources
PubMed1982

Chlordecone neurotoxicity: a brief overview.

Chlordecone or Kepone is a polycyclic chlorinated hydrocarbon insecticide that produces hyperexcitability, tremor, and other signs of nervous system toxicity. In addition, chlordecone has estrogenic-like effects and disturbs neuroendocrine function. Studies at the neurochemical level indicate that chlordecone inhibits neurotransmitter uptake; steady-state levels of biogenic amines are generally resistant to chlordecone, especially in mice. At the subcellular level, chlordecone may destabilize membrane function by altering energy metabolism and/or the disposition of ions required for neural transmission.

Animals↗
PubMed1982

Effects of gestational and perinatal exposure to chlordecone (Kepone) on the neurobehavioral development of Fischer-344 rats.

Fischer-344 rats were exposed throughout gestation and the first 12 days of lactation to 1 or 6 ppm chlordecone via the maternal diet. Exposure to chlordecone had no effect on maternal weight gains after gestation nor did it affect birth weights, litter sizes, or sex ratio of the litters. Offspring tested at 30 and 100 days of age for behavioral performance showed no significant changes in fore- and hindlimb grip strength, spontaneous motor activity, startle responsiveness, or tail flick latencies to thermal stimulation. Negative geotaxis latencies were not affected at 30 days of age, but were increased in males at 100 days of age. Male rats exposed to chlordecone were found to be hypersensitive to the motility increasing effects of 1 mg/kg of apomorphine, which is a dopamine receptor agonist. In another pharmacological challenge with 2 mg/kg of d-amphetamine, a presynaptic releaser or dopamine and norepinephrine, the motility response was not significantly exaggerated in chlordecone exposed rats. These results suggest that fetal and neonatal exposure to chlordecone produces subtle alterations in the neurogenic function of rats.

Animals↗
PubMed1982

Neurobehavioral effects following a single dose of chlordecone (Kepone) administered neonatally to rats.

Male and female Fischer 344 rat pups were exposed to either DMSO or chlordecone (Kepone) by s.c. injection on day 4 postnatally. Chlordecone had transient effects on body weights and resulted in precocial vaginal opening (vaginas open at day 21 of age). At approximately 100 days of age, one half of the animals were trained on a variable interval (VI) 15 sec schedule of food reinforcement. Rates of free operant activity differed during training of the VI and chlordecone-treated females had lower baselines than controls following establishment of baseline responding. Baselines of males were not affected. Chlordecone-exposed rats were affected the same as controls by d-amphetamine (0.25-2 mg/kg) and apomorphine (0.025-0.1 mg/kg). The remaining rats were trained to make a visually cued nose poke response for food in a discrete trial discrimination task. Few differences were noted during acquisition of the task over a three week period. However, marked alterations in responding were observed during two weeks of reversal. These data indicate that a single postnatal injection of chlordecone can produce subtle, long-lasting neurobehavioral changes in rats. The nature of these changes appear to be alterations in their reactivity to novel or changing conditions.

Animals↗
PubMed1982

Neurobehavioral changes in adult Fischer 344 rats exposed to dietary levels of chlordecone (Kepone): a 90-day chronic dosing study.

Chlordecone (Kepone) given in the diet at 10 and 30 ppm for 90 days to adult male Fischer 344 rats produced significant behavioral changes. Rats were tested in a battery of behavioral screening tests for sensorimotor functions at 30, 60, and 90 days of dosing, and 30 days postdosing. Body weight loss was significant by 90 days of dosing with 30 ppm chlordecone; no weight change was seen at the lower dose. Variable effects on grip strength were seen during and after dosing. The magnitude of startle responsiveness to an air puff stimulus was significantly increased by 30 days of dosing in the 30 ppm dose group. Both 10 and 30 ppm doses produced increased responsiveness to an acoustic stimulus by 60 days of dosing. Negative geotaxis and tail flick response to thermal stimulation did not change. By 30 days postdosing, significant behavioral alterations still persisted in startle responsiveness.

Animals↗
PubMed1982

Postsynaptic location of acrylamide-induced modulation of striatal 3H-spiroperidol binding.

The striata of rats were unilaterally lesioned with kainic acid. After two weeks, rats were exposed to 10 doses of acrylamide (20 mg/kg body weight/dose) over two weeks. Binding of 3H-spiroperidol to membranes prepared from unoperated striata, was elevated in acrylamide-exposed rats relative to undosed controls. This differential was not apparent when binding was compared in membranes from kainate-treated striata of acrylamide-treated and untreated rats. A parallel acrylamide treatment of unoperated rats had no significant effect on striatal levels of dihydroxyphenylacetic acid and homovanillic acid suggesting that this neurotoxicant failed to affect the presynaptic events of the dopamine system. Thus, the alterations of the striatal dopamine receptor caused by acrylamide, that have been previously reported, appear to be confined to postsynaptic sites.

Acrylamides↗
PubMed1982

The effects of acrylamide on the behavioral suppression produced by psychoactive agents.

Rats were trained to lever touch for food on a Variable Interval (VI) 15 sec. schedule of reinforcement. Dose-response alteration of VI responding by apomorphine, d-amphetamine, clonidine, and chlordiazepoxide was studied along and in the presence of a dose of acrylamide which, by itself, did not alter VI responding. Pretreatment with 12.5 mg/kg of acrylamide 24 hrs. prior to challenge with psychoactive compounds enhanced the behavioral suppressant effects of apomorphine and d-amphetamine. No significant effect of acrylamide pretreatment on the behavioral effects of clonidine and chlordiazepoxide was observed. These data suggest that acute exposure to acrylamide increases responsiveness to agents that act directly on dopamine (DA) receptors or indirectly by releasing DA. This change in responsiveness to apomorphine and d-amphetamine may be related to the effects of acrylamide on the affinity or density of the DA receptor.

Acrylamides↗
PubMed1982

Postpartum exposure to triethyl tin produces long-term alterations in responsiveness to apomorphine.

Male and female rat pups were exposed to a single dose of triethyl tin (TET) or ethanol vehicle on day 5 postnatally and tested for responsiveness to apomorphine as adults. TET-exposed animals displayed an increased response to the stereotypic effects of 1 mg/kg of apomorphine. Female rats exposed neonatally to TET had decreased baseline rates of responding on a food reinforced variable interval (VI) 15 sec. schedule, while TET-exposed males were found to have increased baseline rates relative to controls. The rats maintained on a VI 15 sec. schedule were given various doses of apomorphine (0.0312-0.25 mg/kg, s.c.). Neonatal exposure to TET had no effect on the disruptive effects of apomorphine on VI 15 sec. responding. These data show an altered responsiveness of TET-exposed animals to higher doses of apomorphine (1 mg/kg), but not to lower doses of apomorphine (0.0312-0.25 mg/kg). The present data are in accord with the hypothesis that one of the long-term consequences of neonatal exposure to TET might be an alteration in the responsiveness of the dopamine system.

Animals↗
PubMed1981

Neurotransmitter receptors in brain regions of acrylamide- treated rats. I: Effects of a single exposure to acrylamide.

A single oral dose of acrylamide (25 or 50 mg/kg) increased the level of striatal 3H-spiroperidol binding in six week old male rats. This enhanced dopamine receptor activity was specific since treatment caused no significant changes in glycine, serotonin, and muscarinic cholinergic binding. At the highest acrylamide dose tested (100 mg/kg), elevations of the medullary glycine and frontal cortical serotonin receptors were also found. Pretreatment of animals with a blocker of hepatic mixed function oxidase (SKF 525a) or a thiol blocker (methylmercuric chloride) prevented the acrylamide-induced elevation of striatal spiroperidol binding, indicating that the causative agent was a secondary metabolite of acrylamide. Apomorphine-induced motility was significantly attenuated by 24 hr predosing with acrylamide, suggesting a change in the sensitivity of the dopamine receptor. The behavioral relevance of observed biochemical changes was thus shown by the altered response of treated animals to apomorphine.

Acrylamides↗
PubMed1981

Neurotransmitter receptors in brain regions of acrylamide- treated rats. II: Effects of extended exposure to acrylamide.

Acrylamide was administered orally to 6 week old male rats in ten doses, spread over a two week period. At the two lower doses (5 and 10 mg/kg, total dose 50 and 100 mg/kg) effects on neurotransmitter receptor sites appeared confined to the striatum where both the dopamine and muscarinic acetylcholine receptors exhibited enhanced binding twenty four hours after the last acrylamide dose. Other receptor sites within the frontal cortex, cerebellum, and medulla were not significantly altered. At the highest dose (20 mg/kg, given ten times), increases were also found for frontal cortical serotonin, medullary glycine, and cerebellar GABA receptor sites. The only unaffected receptor found was the cortical site for benzodiazepene. One week after the final acrylamide dose, the intensity of binding of all ligands studied was not significantly different in treated and control groups. Thus, effects appeared reversible. Since striatal membrane protein concentration was reduced by treatment of rats with acrylamide, the observed increased in activity of muscarinic receptors could be best accounted for in terms of loss of striatal non-receptor protein rather than increased binding. However, the magnitude of increased striatal 3H-spiroperidol binding in treated animals suggested an increase in overall binding capacity. An effect on dopamine neurons was also suggested by a decreased responsiveness to apomorphine in rats treated with acrylamide at 10 mg/kg for 10 successive days; however, the effect had dissipated by 8 days after the final injection of acrylamide.

Acrylamides↗
PubMed1981

3,4,3',4'-Tetrachlorobiphenyl given to mice prenatally produces long-term decreases in striatal dopamine and receptor binding sites in the caudate nucleus.

Pregnant CD-1 mice were given 32 mg/kg of 3,4,3',4'-tetrachlorobiphenyl (TCB) or corn oil vehicle, by gavage, on days 10--16 of gestation. At 1 year of age, the offspring were tested for spontaneous motor activity; the mice were then killed and dopamine (DA) levels and specific DA receptor binding were measured in the corpus striatum. Mice exposed to TCB in utero had elevated levels of motor activity, which were associated with decreased DA levels and DA receptor binding sites. The results indicate that in utero exposure to TCB might permanently alter the development of striatal synapses.

Animals↗
PubMed1981

The neurotoxicity of acrylamide: an overview.

This paper summarizes recent research conducted on the neurotoxicity of acrylamide. Of particular interest is research concerning the possible effects that acrylamide might have on the central nervous system. Neurochemical and psychopharmacological studies indicating that acrylamide affects neurotransmitter systems involved in the mediation of behavior are reviewed. Needs for future research are discussed.

Acrylamides↗
PubMed1981

The effects of postpartum exposure to triethyl tin on the neurobehavioral functioning of rats.

Male and female Fischer rat pups received sc injections of 1.5 or 3 mg/kg of triethyl tin bromide (TET), ethanol vehicle or distilled water on day 5 postpartum. At 21, 28, 60, and 90 days of age, the rats were weighed and assessed in a battery of tests which included fore- and hindlimb grip strength, negative geotaxis, startle responsiveness and spontaneous motor activity. Animals at 60 days of age were also tested in a two-way shuttle box avoidance procedure. Exposure to TET did not affect body weight at any time during testing, nor did it affect negative geotaxis of grip strength, Startle response to an air puff stimulus was decreased in males and females at 21 and 60 days of age, while no effects were observed at 28 or 90 days of age. Responsiveness to an acoustic stimulus was decreased at 60 days of age only. Spontaneous motor activity of males was increased at 21, and 28 and 60 days of age, while females had elevated activity at 28 and 60 days of age. Relative to ethanol controls, rats of both sexes were significantly hypoactive at 90 days of age. In a two-way shuttle box procedure, latencies to emerge prior to the first trial were elevated in TET exposed male and female rats. The number of discriminated avoidance responses made during a 60 trial session was decreased in females receiving the 3 mg/kg dose. Activity during the intertrial interval was not affected. A single postnatal exposure to TET can produce long-term alterations in the sensorimotor capabilities of rats; the effect appears to occur equally in both sexes and is independent of toxicant-induced body weight changes.

Aging↗
PubMed1981

Neonatal exposure to monosodium glutamate alters the neurobehavioral performance of adult rats.

On days 1-15 postpartum male and female Sprague-Dawley derived CD strain pups were dosed sc with either L-glutamic acid (MSG) (2-3.5 mg/g), 13% or 0.85% saline and tested at 67 and 102 days of age. At both periods, the body weights of MSG exposed males were less than the 13% exposed isosmotic controls. MSG exposed females, however, appeared to be obese compared to their controls at 102 days and exhibited a 50% incidence of tail-automutilation. Exposure to MSG did not affect the startle responsiveness of males or females to an acoustic startle stimulus. The startle responsiveness of females to a tactile air puff stimulus was significantly depressed in amplitude at 67 and 102 days; the response on the males at 67 days of age was also decreased, but the effect was not statistically significant. Fore- and hindlimb grip strength assessments indicated that MSG exposed females, at 102 days, had greater hindlimb grip strength. Forelimb grip strength was not affected in either sex. Tail flick latencies to a thermal stimulus were significantly elevated at 67 and 102 days of age in both MSG exposed sexes. Relative to the isosmotic control group, spontaneous motor activity of MSG exposed animals was found to be consistently lower. Exposure to MSG did not, however, change the responsiveness of either sex to the motor activity stimulating effects of a d-amphetamine challenge (0.3-3 mg/kg). These results indicate that postnatal exposure to MSG produced measurable, long-term behavioral and somatic alterations in female and, to a lesser degree, male rats.

Analgesia↗