A gas-liquid chromatographic assay using electron-capture detection was developed for the quantitation of 3,3',4,4'-tetrachlorobiphenyl (TCBP) in the serum, urine, brain, liver, adipose tissue, and feces of the rat. The sample preparation involves extraction of 3,3',4,4'-TCBP with hexane under neutral or alkaline conditions (and washing with concentrated acid for feces only). Aqueous standards are used for calibration of the assay, except for adipose tissue. The lower limit of quantitative sensitivity of the assay for 3,3',4,4'-TCBP is 25 ng/mL for serum and urine and 125 ng/g for brain, liver, adipose tissue, and feces, which can be extended to 5 ng/mL and 25 ng/g, respectively, by analyzing a larger aliquot of the hexane extract. The overall accuracy is greater than 95% for serum, urine, brain and feces and 86% for liver, and the within-day coefficient of variation does not exceed 8.6%. 3,3',4,4'-TCBP was administered orally to adult, female, Sprague-Dawley rats in the dosage regimens: 0.2, 0.5 and 2 mg X kg-1 X day-1 for 10 days and 5 mg X kg-1 X day-1 for 4 days. 3,3',4,4'-TCBP distributed preferentially into adipose tissue and liver, where the xenobiotic concentration was greater in adipose tissue. The adipose tissue and hepatic 3,3',4,4'-TCBP concentrations were dependent on both the absolute dose and dosing schedule of the xenobiotic. Only trace concentrations, usually below the lower limit of quantitation, were detected in the serum, brain and kidney. Fecal excretion of 3,3',4,4'-TCBP was greater than urinary excretion for the 5 mg X kg-1 X day-1 X 4-day regimen.

Administration, Oral↗

PubMed1981

Plasma free and total tryptophan, blood serotonin, and the hyperactivity syndrome: no evidence for the serotonin deficiency hypothesis.

Total and free plasma tryptophan and plasma cortisol levels were determined for children diagnosed as hyperactive or learning disabled and in normal siblings of these subjects. No differences were observed among the groups on any of the dependent variables related to a number of parameters measured for the hyperactive children such as degree of hyperactivity, presence of food allergies, favorable response to methylphenidate, and brain dysfunction. Moreover, in further comparisons no differences were found between hyperactive and age-matched controls on these variables as well as blood serotonin, nor were any differences found for a group of hyperactive children between placebo and methylphenidate trials. These data do not support earlier suggestions of a serotonin deficiency in hyperactive children.

Attention Deficit Disorder with Hyperactivity↗

PubMed1980

Enhancement of tyrosine hydroxylase activity by Oxotremorine does not affect sleep in the rat.

Marked enhancement of tyrosine hydroxylase (TH) activity was observed in the rostral pons of Wistar albino rats, 3 days after a single injection of Oxotremorine. TH activity in other brain areas, and regional levels of norepinephrine, dopamine, serotonin and 5-hydroxyindoleacetic acid were unaffected. Enhancement of TH activity did not affect length or number of REM episodes, or the amount of REM occurring in 24 hr. REM occurrence did not, thus, vary in accordance with activity of the rate-limiting enzyme for catecholamine synthesis. These data suggest that, although REM may reflect neuronal protein synthesis, REM is not part of a mechanism regulating the activity of enzymes in the pontine CA synthesis pathway.

Animals↗

PubMed1980

A comparison of the porphyrin-inducing activity of barbiturates and benzodiazepines in chick embryo liver cells.

Five benzodiazepines, flurazepam, nitrazepam, diazepam, oxazepam, and chlordiazepoxide, have been tested for porphyrin-inducing activity in chick embryo liver cell culture and for delta-aminolevulinic acid (ALA) synthetase inducing activity in the 17-day-old chick embryo. Flurazepam and nitrazepam were found to have considerably lower potency than secobarbital whereas diazepam, oxazepam, and chlordiazepoxide were less potent than phenobarbital in these test systems. The following conclusions were arrived at. (1) A hypnotic dose of flurazepam or nitrazepam would be less likely than a comparable dose of secobarbital to increase ALA synthetase activity in a patient with hereditary hepatic porphyria. (2) A sedative dose of diazepam, oxazepam, or chlordiazepoxide would be less likely than a comparable dose of phenobarbital to increase ALA synthetase activity in a patient with hereditary hepatic porphyria. (3) The benzodiazepines, although apparently less likely to precipitate an attack than barbiturates, should be used with great caution in porphyria patients.

5-Aminolevulinate Synthetase↗

PubMed1979

Postnatal effects of maternal nicotine exposure.

Rats were given dilute nicotine solutions as their only source of drinking water while control rats received distilled water. Two months after the start of treatment the rats were mated. At birth litters born to nicotine treated rats were either left with the dams until weaning (nicotine group) or cross-fostered to control dams (cross-fostered nicotine group). Both parents and offspring were tested when the pups were 60 to 80 days of age. The drug-treated adult rats showed a marked reduction in body weight gain during the period of drug treatment. The dams were more active during the day and exhibited a reduced plasma corticosterone response to stress. Male but not female offspring of nicotine treated rats were significantly lighter at birth than control males. Offspring in the nicotine group showed an increased spontaneous motor activity in the light which was not prevented by cross-fostering to control dams at birth. The results support the hypothesis that pre-natal exposure to nicotine causes significant changes in behavior in later life.

Adrenal Glands↗

PubMed1978

Effect of stress on brain histamine.

Stress of short duration (5 min) resulted in a significant increase in plasma corticosterone level and a significant decrease in the midbrain histamine concentration in rats. Exposure to 15 min stress caused a significant elevation in the hypothalamic histamine level. Stress of longer duration (30 or 60 min) did not affect hypothalamic, cortical or midbrain histamine concentration although plasma corticosterone level remained elevated. Repeated exposures of rats of 15 min stress did not significantly alter histamine concentration of any of the brain regions studied. Plasma corticosterone concentration was only 28% of that observed in animals exposed to single 15 min stress. Present data suggest a role of brain histamine in response to stress.

Animals↗

PubMed1978

Altered 5-hydroxyindole concentrations in brain regions of rats treated with chlorpromazine in infancy.

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Aging↗

PubMed1978

Tyrosine hydroxylase activity in brain regions after intraventricular 6-hydroxydopamine in the neonatal rat.

Intraventricular 6-OHDA treatment to newborn rats produced a marked reduction in tyrosine hydroxylase activity in most brain regions at maturity which correlated moderately well with the catecholamine levels. However, those regions in which NE levels were increased did not show a corresponding increase in total tyrosine hydroxylase activity. There was a much better correlation between NE levels and the particulate form of tyrosine hydroxylase which has been suggested to be the more functionally active form of the enzyme.

Animals↗

PubMed1977