Effects of delta 9-tetrahydrocannabinol on foot shock-induced aggression in rats.
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Biomedical subjects
Publications and source records attributed to B Ghosh.
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The effect of cocaine, over a dose range of 2--60 mg/kg, i.p., on self-stimulation (SS) behavior was studied in rats with electrodes either in the posterior hypothalamus (PH, monoaminergic) or the area ventralis tegmentum (A10, dopaminergic). The drug increased SS behavior with peak effects at 30 mg/kg in PH rats and 20 mg/kg in A10 rats. Azaperone (an alpha-adrenergic blocker) and haloperidol (an antidopaminergic neuroleptic) given at doses that did not affect baseline SS responses reduced cocaine-induced enhancement of SS in both PH and A10 rats, showing the involvement of both noradrenergic and dopaminergic mechanisms in SS behavior. A scopolamine dose that itself facilitated SS responding enhanced the effect of cocaine on this behavior, thus suggesting an additional involvement of cholinergic mechanisms in cocaine effect.
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Twelve medicinal herbs were bioassayed to correlate a high incidence of esophageal carcinoma in natives of different places with their habitual consumption of these products. Outbred NIH Black rats were given 72 weekly sc injections of the total aqueous extracts of the plant materials. The tanninrich plant extracts from Areca catechu and Rhus copallina produced local tumors in 100 and 33%, respectively, of the experimental animals. Other materials included Diospyros virginiana and extracts from plants not rich in tannins. Diospyros and extracts of Sassafras albidum and Chenopodium ambrosiodes were tumorigenic in over 50% of the treated animals.
The metabolism of ascorbic acid was studied in hydrazine-treated rats. Hydrazine was administered i.p. at a dose of 1.28 mg/day (20% LD50) for each 100 g body weight for 7 days. Hydrazine administration at the present dose did not appear to have an effect on the total ascorbic acid level of liver, kidney, spleen and testis. The adrenal and plasma total ascorbic acid levels were, however, elevated. The activity of liver D-glucuronoreductase and that of liver and kidney dehydroascorbatases were diminished after hydrazine administration. The changes in the activities of liver enzymes were accompanied by a fall in the reduced ascorbic acid level and an elevation in the dehydroascorbic acid level. The uronolactonase activity of liver, on the other hand, remained independent of hydrazine treatment. It has been suggested that hydrazine treatment at the present dose reduced the biosynthesis of L-ascorbic acid from D-glucuronolactone as substrate. In spite of diminished synthesis, the normal level of total ascorbic acid in the liver of hydrazine-treated rats was maintained by reducing the degradation of L-ascorbic acid. The rise in the plasma total ascorbic acid level after hydrazine treatment was ascribed to reduced catabolism and urinary excretion of ascorbic acid, while the elevation in adrenal total ascorbic acid level might result from increased uptake of ascorbic acid by the gland from blood or from nonfunctional accumulation.
In an attempt to correlate the high incidence of esophageal carcinoma in natives of certain places with their habit of using herbaceous folk medicines, we performed bioassays of several plant extracts and the fractions prepared from them. Fourteen extracts and fractions from 6 plants were injected sc into NIH Black rats. The tannin fractions from Quercus falcata pagodaefolia, Diospyros virginiana, and Camellia sinensis were very active and produced tumors at the injection site in 66% or more of the treated animals. Tannin fractions from 3 other plants and total aqueous extracts from 5 to 6 tested plants were also tumorigenic rats. The induced tumors were malignant fibrous histiocytomas similar, if not identical, to those encountered in humans. The experiment indicated a possibility of induction of tumor in man by the tested plant materials.
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The effects of administration of L-lysine on total ascorbic acid level of various tissues and plasma of rats were studied. The biosynthesis of L-ascorbic acid by the liver tissue was also followed. L-lysine was administered at a dose of 88.3 mg day-1 (20% of LD50) for each 100 g body weight for 14 days. L-lysine administration at the present dose elevated the total ascorbic acid level of liver, kidney, testes, spleen and brain tissues. The plasma total ascorbic acid level was also elevated. The synthesis of L-ascorbic acid from both D-glucuronolactone and L-gulonolactone by the liver was, however, reduced after L-lysine administration. It has been suggested that L-lysine administration at the present dose altered the plasma amino acid pattern which in turn impaired the in vivo synthesis of tissue proteins and, consequently, the synthesis of apoproteins of ascorbic acid-synthesizing enzymes, the D-glucuronoreductase and L-gulonooxidase, were reduced. The elevation in the total ascorbic acid level of extra-hepatic tissues and plasma after L-lysine administration was ascribed to the reduced catabolism and diminished urinary excretion of ascorbic acid.
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Genetic analysis of 170 subjects in 11 extended Amish families revealed evidence for linkage of five markers in chromosome 5q31.1 with a gene controlling total serum IgE levels. No linkage was found between these markers and specific IgE antibody levels. Analysis of total IgE within a subset of 128 IgE-antibody-negative sib pairs confirmed evidence for linkage to 5q31.1, especially IL4 (p = 4 x 10(-6)). These and other data suggest that IL4 or a nearby gene regulates IgE production in a non-antigen-specific (noncognate) fashion and provide evidence for a possible link between asthma and the IL4 gene.
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