Alcohol and drug research最新文献

The interaction of a representative benzodiazepine, flurazepam, and ethanol has been assessed in ICR albino mice. Tests done included loss of "rotarod" performance, light sedation, deep sedation, loss of righting reflex, anesthesia, and lethality. LD50 and ED50s were plotted as isobolograms (plots of equieffective dose combinations). Data for anaesthesia and lethality showed little or no interaction between the two drugs. In contrast, the four motor and behaviour tests showed synergism, especially with higher doses of ethanol (over 2 g/kg) for righting reflex, and (over 1.5 g/kg) for deep sedation. Synergism occurred over all doses for light sedation and rotarod performance. It is expected that concurrent use of benzodiazepines and ethanol can result in a significantly higher accident risk in humans, but little additional risk of death from simple overdose.

The effects of acute low-dose maternal alcohol exposures were investigated in C57B1/10J mice offspring. Pregnant mice were randomly placed into three alcohol groups and were injected twice intraperitoneally on gestation day 7, 0 hours and gestation day 7, 4 hours, with one of the following dosages of 25% alcohol: Group 2 received 1.25 Gm/Kg body weight; Group 3 2.50 Gm/Kg body wt.; Group 4 3.75 Gm/Kg body wt. A control group (Group 1) received .015 ml/gm body wt. of physiological saline. At birth all offspring were weighed and observed for any gross physical abnormalities. On day 25, all female offspring and mothers were sacrificed. The male pups were maintained until day 61. On day 61, the male pups were placed in individual metabolic cages where food and water consumption, and urine excretion were monitored for 24 hrs. On day 62, these animals were sacrificed. Blood was drawn for serum calcium (Ca) and phosphorous (P) determination. Brains, kidneys, testes, hearts and thymus glands were removed and weighed. Ca and P levels were also measured in the urine. No significant difference in litter size and fetal weight was obtained among the four groups. There was no evidence of physical abnormalities in the alcohol groups compared to the control one. The 62 day old pups from all three alcohol groups had significantly lower serum and urine levels of Ca and P than the control group, with the lowest values recorded for Group 4. There was no significant difference in final body weight but small organ size differences were observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Using the technique of within-family selective breeding, we have generated mouse lines that differ genetically in sensitivity to the acute hypothermia induced by injection of 3 g/kg ethanol (EtOH). After 5 generations of selection, the difference in maximal hypothermic response between COLD and HOT lines was 1.6 degrees C in the first replicate and 1.2 degrees C in the second replicate. Estimates of realized heritability were h2 = .17 in each replicate. No differences in EtOH metabolism have developed, so the differences between HOT and COLD mice are presumably in neurosensitivity. These lines of animals should be useful for studying the biological mechanisms underlying neurosensitivity to EtOH. In conjunction with other selectively bred lines, they should improve our understanding of the genetic relationships among EtOH neurosensitivity, tolerance and physical dependence.

Fifteen drug-abusing doctors each directed their psychiatrist to mail to their licensing boards a pre-prepared license-surrendering letter if any of a series of urine samples contained drugs. The doctors also received other, individualized treatments. Profound reductions in drug use occurred. Seven patients did not relapse at all during the 2-year (average) follow-up, and 4 others experienced only very brief relapses. Four licenses were suspended temporarily by contract, but 6 were suspended or revoked for other reasons. Other reports on such patients reveal some adverse outcomes, and two of these patients had adverse outcomes after relapsing and discontinuing treatment.

Many drugs of abuse (opiates, cocaine, amphetamine, caffeine) modulate or interact with neurotransmitter systems in the brain (e.g., opiate, dopaminergic, adrenergic, purinergic), generally in an inhibitory fashion. However the cellular mechanisms underlying these interactions are varied and often not well-characterized. A summary of the literature on the neuromodulation of two amino acid neurotransmitters (gamma-aminobutyric acid, glutamate) by these drugs and their analogs may contribute to the understanding of the mechanisms underlying inhibitory neuromodulation. In addition, the types of experiments needed to alleviate some of the problems in this area are outlined.

Seven pregnant ewes were prepared with open-ended tracheal T tubes and with catheters in maternal femoral artery and in central circulation of fetus. Several days postoperatively, at 129-132 days gestation, ewes inhaled smoke from one marijuana cigarette containing 3.19% delta-9-tetrahydrocannabinol (delta-9-THC). Smoke was produced continuously in a hand-held chamber and delivered to the protruding arm of the tracheal tube. Samples of maternal and fetal blood were taken during the 8-10 minute smoking period and at intervals up to 24 hours. Delta-9-THC was detected in maternal plasma at 3 minutes and peaked at 10 minutes. Fetal plasma delta-9-THC reached detectable levels in 5 animals by 10 minutes. Maximum mean level was reached at 90 minutes and remained nearly constant until the fourth hour. Fetal delta-9-THC levels remained lower than maternal levels at all times. The terminal half-life of delta-9-THC in fetal and maternal plasma exceeded 10 hours.

In an attempt to investigate whether a relationship exists between exposure to stressful stimuli and the consumption of CNS stimulants, rats were given continuous access to an 0.1% saccharin solution and either d-amphetamine (AMP), methamphetamine (MET) or phenylpropanolamine (PPA) at two concentrations. Animals were exposed to either isolation/novel environment or immobilization stress repetitively over a two week period on an irregular/unpredictable schedule. No differences were seen between control (non-stressed) and stressed animals with respect to the volume of AMP, MET or PPA consumed either during stress or in two weeks post-stress. All three drugs failed to demonstrate any oral reinforcing properties as evaluated by positional perseveration. In contrast to earlier work using ethanol, the data suggests that stress has very little influence over the oral ingestion of phenethylamines.

Development of tolerance to ethanol was examined using heart rate as a measure. Ethanol-treated rats were infused IG with 8-11 g/kg/day (in 3 divided doses), control rats received similar infusions of either equicaloric dextrin-maltose or water (equivolumetric) for a period of 17 days. On days 1, 5, 9, 13 and 17 of treatment heart rate was recorded before and at 10, 20 and 30 minutes after injection of a challenge dose of 2 g/kg ethanol, dextrin-maltose or water. The tachycardia produced by ethanol increased with days of chronic treatment to a maximum on the 9th day of treatment. Significant tolerance to the tachycardia was evident only on the 17th day of treatment. Neither control showed significant changes in heart rate.