Modulation of alpha 1-and alpha 2-adrenoceptor binding sites in the brain of audiogenic seizure susceptible mice (DBA/2J).

The binding of [3H]dihydroalprenolol ([3H]DHA), [3H]prazosin and [3H]clonidine was assayed in whole brain and various brain regions of audiogenic seizure (AS) susceptible DBA/2J (D2) mice aged 10, 24 and 50 days (i.e. before, during and after their period of AS susceptibility, respectively) and in age-matched C57BL/6J (B6) controls. In whole brain, at 24 days, [3H]DHA binding was similar in the two strains, while the binding of [3H]prazosin and [3H]clonidine was significantly lowered in D2 mice. No difference could be detected in 10 and 50 day old mice with any of the ligands. Regional studies indicated an involvement of the cerebral cortex, the olfactory bulbs and the brain-stem. alpha- (but not beta-)adrenoceptor changes were concomitant with the AS susceptibility period. These changes were unevenly distributed in the brain of D2 mice; they suggest that alpha 1- and alpha 2-adrenoceptor subtypes might play different roles in the AS of the D2 mouse strain.

Altered postnatal ontogeny of alpha 1- and alpha 2-adrenoceptor binding sites in the brain of a convulsive mutant mouse (quaking).

Binding assays of [3H]dihydroalprenolol ([3H]DHA), [3H]prazosin and [3H]clonidine have been performed on whole brain (minus cerebellum) homogenates of the convulsive mutant mice quaking (qk) and the controls of the same strain (C57BL/6J:B6). In 70-day-old mutants (which fully exhibit the qk convulsive phenotype), the binding of [3H]DHA to beta-adrenoceptor binding sites was not different from the controls, whereas the binding capacities of [3H]prazosin and [3H]clonidine to alpha 1-and alpha 2-adrenoceptor sites, respectively, were greatly enhanced. The biphasic ontogenic pattern of alpha 2-adrenoceptors had a greater amplitude in the brain of 30- to 90-day-old mutants than in the corresponding B6 controls. In mutants younger than 30 days or older than 90 days, the number of alpha 2-adrenoceptor sites was not modified. The number of alpha 1-adrenoceptor binding sites was increased in the brain of the mutants, only in animals older than 70 days. In younger mice, the postnatal modulation of alpha 1-adrenoceptor sites was identical to the controls. Regional studies were performed in 70-day-old mice. [3H]clonidine binding was increased in the brainstem of the mutants, and to a lesser extent in the cerebral cortex, while it was slightly diminished in the hypothalamic area. [3H]prazosin binding was also increased in the brainstem of the mutants, and decreased in the olfactory bulbs. Our results suggest that the convulsions of the qk mutants are selectively associated with modifications of alpha- and not beta-adrenoceptor binding sites.(ABSTRACT TRUNCATED AT 250 WORDS)

[Induction of cytochrome P 450 by phenobarbital in cats]. / Induction du cytochrome P 450 par le phénobarbital chez le chat.

Phenobarbital administration to the Cat an animal hypersensitive to the actions of many toxic substances or to physiological compounds such as hormones, does not produce cytochrome P 450 induction. Consequently, hepatic storage of retinol remains unchanged. The specific and original characteristics of the Cat in this field are underlined by these results.

[Joint effects of dietary protein levels and vitamin A additions on the induction of cytochrome P450 by DDT in rats]. / Influences conjuguées du taux de protéines du régime et de l'apport de vitamine A sur l'induction du cytochrome P 450 par le DDT chez le rat.

A 5 P. 100 level of protein from casein in a diet does not allow vitamin A to modify significantly induction of cytochrome P 450 on the Rat receiving or not receiving DDT. When the protein increases to a 15 p. 100 level, the induction is better providing vitamin A is to be given. If protein and vitamin A are necessary for cytochrom P 450 induction, an increase of protein level remains inefficient without vitamin A.

[Difference in the sensitivity of the hamster and the rat to the effects of long-term administration of ethylenethiourea]. / Différence de sensibilité du hamster et du rat vis-à-vis des effets de l'administration à long terme de l'éthylène thiourée

Rats and hamsters were fed ETU at levels of 0, 5, 17, 60, 200 mg/kg in the diet. Body weights, food consumption, seric enzyme activities (GPT, alkaline phosphatase), hepatic enzyme activities (GPT, alkaline phosphatase G6PDH), cholesterolemia, thyroid weight and others organs, histology were the criteria studied. ETU was found causing hypercholesterolemia for the 2 species at 5 mg/kg dietary levels. Thyroid impairement is predominant in rat and hepatic impairment is predominant in hamster. ETU was found to be not carcinogenic for hamsters even at 200 mg/kg level and carcinogenic for rats at 60 mg/kg level for males and 200 mg/kg level for females.

[Induction of cytochrome P450 and vitamin A. Study in swine under the influence of DDT]. / Induction du cytochrome P450 et vitamine A. Etude chez le porc sous l'influence du DDT

DDT induces in young Pigs a rise of hepatic level of cytochrome P 450 and a concomitant decrease of the hepatic "reserve" of retinol. The amplitude of these effects varies according to the hepatic lobe submitted to analysis.

Use of the golden hamster in toxicology.

The choice of an appropriate species and strain of laboratory animal is one of the toxicologist's major concerns. The biochemical, anatomical, and other characteristics of the golden hamster which make it a valuable though limited tool in toxicologic research were reviewed. The effects of organochloride insecticides on rats, mice, and hamsters were compared. These substances can be classified into 3 groups based on the hamster's sensitivity to acute toxic effects. The hamster is so insensitive to DDT and its immediate metabolites, DDD and DDE, that an LD50 cannot be established, whereas the hamster's sensitivity to other organochlorides varies when compared with mouse and rat sensitivity. The long-term effects of sub-lethal doses of organochloride insecticides on biochemical pathways were evaluated, particularly on liver function. The details of the induction of drug-metabolizing enzymes in the hamster and in the rat were also explored.

[Research on the modalities and mechanisms of toxic action of organochlorine insecticides. II. Long term toxicity effects of DDT in hamsters]. / Recherches sur les modalités et les mécanismes d'action toxique des insecticides organochlorés. II. Etude chez le hamster des effets de toxicité à long terme du DDT

18 months DDT feeding showed no carcinogenic potentiality in hamster even with the dose of 1 g/kg of DDT in the diet.