Associative control of tolerance to the sedative effects of a short-acting benzodiazepine.

The role of Pavlovian conditioning in tolerance to the depressant effect of a benzodiazepine (midazolam) on the ambulatory activity of rats was examined. The depression of activity by low doses (1.0 and 4.

Role of calcium on TPA-induced secretion of ACTH and PGE2 by pituitary cells: effect of dexamethasone.

In pituitary cells in primary culture, ACTH and PGE2 secretions can be simultaneously stimulated by TPA, in the presence of Ca2+. However, whilst PGE2 secretion is under an absolute requirement for Ca2+, ACTH secretion is not. Both secretions are inhibited by dexamethasone but to various extents: PGE2 release is abolished in the presence of dexamethasone whilst only 35% of the TPA-induced ACTH release is sensitive to dexamethasone.

Effect of a new topically active antiandrogen (RU 38882) on the rat sebaceous gland: comparison with cyproterone acetate.

RU 38882 is a new antiandrogen. When given by subcutaneous or oral route, RU 38882 is about 25 times less potent than cyproterone acetate. However, when applied topically to the intact rat skin, RU 38882 (0.

Antiandrogenic activity of a series of des-A-steroid derivatives.

In the search for new antiandrogens, a number of des-A-steroids were prepared by condensation of Grignard reagents with lactone 3. From the resulting key intermediates 5, various structural modifications were performed such as the introduction of an additional unsaturation to afford dienones 8 and aromatic derivatives 10 or the introduction of an alkyl substituent mostly in position 10 (11-13) but also in some cases in position 16 (22). In addition, 13-ethyl analogues were also prepared from lactone 4.

Transient transcriptional inhibition of the transferrin gene by cyclic AMP.

Transferrin mRNA content and gene transcription rate were measured in the liver of rats submitted to iron overload or depletion, castration, treatment with sexual steroid hormones, glucagon and cyclic AMP. The influence of puberty in males and females and of pregnancy was also analysed. Glucagon and cyclic AMP reduced mRNA level by about 50% at the 12th hour of treatment and transferrin gene transcription by as much as 95% at the 30th minute of drug infusion, with a secondary increase of the transcription rate for a protracted treatment.

RU 16117, an orally active estriol-like weak estrogen.

RU 16117, the 11 alpha-methoxy derivative of ethynyl estradiol, is an orally active weak estrogen potentially effective in the treatment of estrogen-deficiency in postmenopausal women (climacteric symptoms and severe osteoporosis). Biochemical studies have shown that RU 16117, like estriol, possesses the properties characteristic of a partial estrogen agonist/antagonist. RU 16117 binds to the cytosol estrogen receptor (ER) to form a complex which dissociates much faster than the estradiol complex.

Contextual control of the extinction of conditioned fear: tests for the associative value of the context.

Four conditioned suppression experiments examined the influence of contextual stimuli on the rat's fear of an extinguished conditioned stimulus (CS). When rats received pairings of a CS with shock in one context and then extinction of the CS in another context, fear of the CS was renewed when the CS was returned to and tested in the original context (Experiments 1 and 3). No such renewal was obtained when the CS was tested in a second context after extinction had occurred in the conditioning context (Experiment 4).

Substituted derivatives of A-nor-5 alpha-androstane and A-nor-5 alpha-estrane--structure and affinity for hormonal receptors.

The interactions of A-nor-5 alpha-androstane and A-nor-5 alpha-estrane derivatives with the estrogen and androgen receptors, have been evaluated by measuring their relative binding affinities (RBAs), under two sets of incubation conditions in order to discriminate between potent agonists from weak agonists with potential antagonist activities. Surprisingly some of these compounds which do not possess a phenolic hydroxyl group interact somewhat markedly with the estrogen receptor. This interaction is characteristic of weak estrogens, with potential anti-estrogenic activity (RBA values decreasing when increasing time and temperature of incubation).

Relative potency of foods and drinks as targets in aversion conditioning.

The potency of food stimuli as targets in aversion learning was examined using an interference paradigm. In the first study, foods interfered with liquid aversions but liquids did not interfere with food aversions. In the second study, food aversions were found to be resistant to interference by other foods.

Regeneration of motor axons in crayfish limbs: distal stump activation followed by synaptic reformation.

Severed distal stumps of limb motor axons in the crayfish Procambarus clarkii remain ultrastructurally intact for at least 2-3 ms after being severed from their cell body. Initial regeneration of a motor axon is associated with the appearance of up to 200 small profiles (satellite axons) having no glial sheath adjacent to the large surviving stump for about 1 cm distal to the lesion at 4-5 wks postoperatively. These satellite axons are seen 2-4 cm distally at the target muscles 3-4 ms postoperatively.

Effects of RU16117, an orally active weak oestrogenic compound, in postmenopausal women.

Daily oral administration of 1, 3 or 10 mg of RU16117 (11 alpha-methoxy ethinyl oestradiol) to normal postmenopausal women led to a progressive decrease of basal serum LH levels to 60.4 +/- 17.0, 35.

Role of conditioned contextual stimuli in reinstatement of extinguished fear.

If the unconditioned stimulus (US) is presented independently of the conditioned stimulus (CS) following extinction, the conditioned response may be reinstated to the CS. Three experiments are reported that suggest that reinstatement is mediated by conditioning to contextual stimuli that are present during both US presentation and testing. Shocks presented to rats following the extinction of conditioned suppression reliably reinstated suppression to the CS, but only when they were presented in the context in which testing was later to occur.

Effect of estradiol on rat uterus DNA-dependent RNA polymerases. Studies on solubilized enzymes.

DNA-dependent RNA polymerases of immature and castrated rat uteri were studied after estradiol administration. The enzymes were solubilized from either whole uterus homogenate or nuclei and their activities were measured on an exogenous DNA template. alpha-Amanitin was used to distinguish alpha-amanitin-resistant from alpha-amanitin-senitive forms of the enzyme.