Naloxone effects on a nociceptive response of hypophysectomized and adrenalectomized mice.
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Biomedical subjects
Publications and source records attributed to A Goldstein.
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In 30 human subjects, experimental pain was produced by either ischemia or cold-water immersion. In a double-blind procedure, intravenous doses of up to 10 milligrams of naloxone hydrochloride in saline were indistinguishable from similarly administered saline alone. There were no effects on subjective pain ratings, finger plethysmograph recordings, or responses to mood-state questionnaires. These laboratory procedures do not activate any functionally significant pain-attenuating or mood-altering effect of endorphins.
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Heroin addicts who had been maintained for at least three months on LAAM (levo-alpha-acetylmethadol, methadyl acetate) and at least three months on methadone were asked to compare the two drugs on a number of criteria. The responses were highly selective, indicating that a desire to please the investigators was not an important factor. Overwhelmingly, the majority of patients reported that LAAM provided better heroin "blockade", that it was more effective in reducing craving, and that actual use of heroin was less on LAAM than on methadone. In other respects, such as sexual performance, sleep, and appetite, most patients perceived no difference between the drugs. In no respect was methadone preferred by a majority, although methadone was viewed more favorably on some criteria by some patients. These findings indicate that for most heroin addicts LAAM will be an acceptable maintenance drug.
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The author describes a simple method to rapidly and accurately measure the densities of randomly shaped CT phantom materials.
Swiss-Webster stock male and female mice were tested for running activity after a 20 mg/kg dose of levorphanol. The best runners and worst runners were then bred. Within each litter, brother-sister pairs with the highest and lowest running activity after a test dose of levorphanol (20 mg/kg) were segregated and bred. This procedure was followed to the F4 generation. Running activity, analgesia and brain catecholamines were studied. The results showed that the "non-running" (NR) trait segregated at the F1 generation, while the "running" (R) trait diverged more slowly. However, by the third generation, the R mice differed significantly from the F0 stock mice. NR mice also did not show locomotor activity when tested with amphetamine. While the NR mice showed reduced running response to levorphanol they were significantly more sensitive than the F0 stock to the analgesic effect. Measurement of brain catecholamines showed no difference between R and NR mice in dopamine or serotonin, but did show a significant increase in norepinephrine in the NR strain.
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The effect of naloxone on the latency of mice to enter a dark box was determined and the study of Jacob et al. (1974) on the effect of naloxone on hotplate behavior was replicated. Mice took significantly longer to enter a dark box after receiving 10 mg/kg of naloxone than did the saline controls. With the hot-plate technique, at all doses (0.1, 0.3, 1, 3, and 10 mg/kg) except the lowest (0.03 mg/kg), naloxone-treated mice jumped from the hot plate significantly sooner than did the saline controls. No effect of naloxone on paw-lick latency was found. All the data confirm the findings of Jacob et al. (1974). The hotplate results suggest that prolonged exposure to a noxious stimulus may be necessary to activate the endorphin system.
Endorphin was found in the pituitary gland of rat, sheep, pig, cow and man. In bovine pituitary, highest concentrations have been found in that part of the posterior lobe containing the pars intermedia, although endorphin was also present in the pars distalis. Analysis by gel filtration and adsorption chromatography suggested that the major endorphins from rat, pig and cow pituitary were similar, with apparent molecular weights in the range 3000-3500 daltons.
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