Alcohol and drug research最新文献

Pregnant C57Bl/10J mice were treated intraperitoneally with alcohol (Group A) or saline (control) on Day 7 of gestation. On Day 7, at 0 hour and again at 4 hour, Group A received 0.020 ml/GM body weight of 25% (v/v) alcohol, while control mice received 0.020 ml/GM body weight of physiological saline. The injection schedule specified corresponds to a specific stage of fetal development, namely gastrulation. On Day 13 of gestation, all animals were placed in individual metabolic cages to monitor both food and water intake and urinary output. The animals were sacrificed on Day 14. Blood was withdrawn and the serum was used for analyses. In addition, resorption sites within the uterine horns were recorded and fetuses examined. Group A animals had significantly lower serum calcium (Ca) than the controls (6.1 +/- 0.7 mG% versus 9.6 +/- 1.6 mG%, P less than .01). By contrast, the same alcohol injected mice had higher serum phosphate (P) than the controls (18.2 +/- 5.9 mG% versus 12.3 +/- 4.0 mG%, P less than .05). Urinary Ca levels were lower (P less than .05) while urinary P values tended to be higher in alcohol injected mothers. Furthermore, Group A mice had litters which were smaller in size, lower in average fetal body weight and had a higher incidence of resorption (18%) than control mice. Examination of the viable fetuses showed that 53% of those from alcohol treated mothers had facial abnormalities while only 12% of the fetuses from the controls looked abnormal. The results indicate that exposure to acute alcohol in this early stage of pregnancy creates disturbances in maternal Ca metabolism, which may be ultimately related to the observed fetal abnormalities.

Several studies have shown that there are differential levels of salsolinol excretion between consumers of varying levels of alcohol. The excreted salsolinol may arise during metabolism of alcohol, reflect endogenous biosynthesis of the compound, or result from ingestion of exogenous salsolinol. A previous study identified that salsolinol excretion in urine distinguished light and heavy social drinkers, who had consumed chocolate (containing salsolinol) in combination with a test dose of alcohol. The present study was designed to examine the relationship between social drinking level and the excretion of salsolinol after ingesting dietary salsolinol alone. Participants were 120 volunteers, balanced for gender, social drinking level (abstainers, light, moderate and heavy), and dose of salsolinol. Urine samples were taken on entry, and at 90 minutes and 3 hours after consumption of chocolate. Analysis revealed a dose effect on salsolinol excretion. There were no main or interactive effects of gender or social drinking on salsolinol excretion. The results indicate that the appearance of salsolinol in urine following dietary consumption alone is insufficient to distinguish alcohol consumption levels in social drinkers.

Plasma met-enkephalin immunoreactive material (ME-IR) concentration was measured in 175 aged subjects (68 males, 107 females). Heavy drinking (1 liter of red or white wine a day, equivalent roughly to greater than 110 g ethanol) was associated with reduced ME-IR concentrations. On the other hand, no correlation was found between plasma ME-IR and other parameters such as blood pressure, age or body weight. These data favor the hypothesis of an involvement of ME-IR in the mechanisms of ethanol action.

The effects of marijuana smoke on maternal respiratory rate and gas exchange were examined in nine chronically instrumented, late gestation ewes carrying singletons. The magnitude of exposure was randomly varied producing peak plasma levels of delta-9-tetrahydrocannabinol (delta-9-THC) ranging from 0 to 161 ng/ml. delta-9-THC levels, respiratory rate and arterial blood gas tensions were monitored before and for two hours after inhalational exposure. When compared to placebo, marijuana smoke produced a dose dependent and sustained decrease in maternal respiratory rate and arterial oxygen tension without evidence of either systemic acidosis or carbon dioxide retention. A logarithmic relationship was observed between the blood level of delta-9-THC and the change in respiratory rate. The change plateaued at 30% of control at levels above 80 ng/ml. However, the relationship between the blood level of delta-9-THC and the change in arterial oxygen tension had a linear fit with a maximum decrease of 45% at a blood level of 160 ng/ml. No change was detected in minute ventilation. Fetal oxygen tension fell significantly and remained depressed after maternal values had returned to control levels. We conclude that, in this species, inhalational exposure to marijuana smoke induces a prolonged maternal ventilation/perfusion imbalance and limits fetal oxygen availability by one or more mechanisms.

Mice were treated with 0.025% alprazolam incorporated into their laboratory chow for periods of one, two, and four weeks. Treated animals gained weight and appeared healthy during treatment, although an increased number of animals were lost in the treatment groups due to cannibalism. When regular food was substituted, alprazolam-treated animals experienced a withdrawal reaction qualitatively similar to that previously observed following similar lengths of treatment with 0.1% diazepam in food. The withdrawal reaction following alprazolam had a faster onset and a shorter time course, and was less intense. In a separate experiment, eight mice were treated with alprazolam for two weeks but were housed singly. This eliminated the cannibalism problem and no animals were lost during the treatment phase; the withdrawal syndrome was similar to that seen in group-housed animals. The model of benzodiazepine dependence in mice would appear to generalize to the entire class of drugs and may permit distinctions to be made between the time-course of withdrawal reactions between the various members of that class.

Intracerebroventricular (icv) administration of neurotensin produced a dose-dependent increase in ethanol sensitivity as measured by blood ethanol concentration at loss of righting reflex in SS/Ibg (SS) but not in LS/Ibg (LS) mice. Central administration of calcium also enhanced ethanol sensitivity of SS and to a lesser extent LS mice. Concurrent icv administration of calcium and neurotensin resulted in an additional enhancement of sensitivity to ethanol over that seen with either substance alone in both mouse lines. A dose-dependent increase in ethanol sensitivity was also produced in response to central administration of beta-endorphin in SS mice. No additional increase in sensitivity was noted following administration of beta-endorphin plus calcium. These results suggest a specific interaction of calcium and neurotensin may be involved in the mechanism through which ethanol elicits intoxication. The difference in response of LS and SS mice to neuropeptide and calcium-induced alterations in ethanol sensitivity may be related to the genetically selected differences to the acute narcotic actions of ethanol in these mice.

The effects of graded doses of a substituted tripeptide analogue of the C-terminal part of oxytocin, D-Pip-Leu-GlyNH2 (DPLG), were investigated on the development of tolerance to the hypothermic effect of and dependence on alcohol in mice. Ethanol injection (4 g/kg i.p.) repeated on 3 consecutive days led to the development of tolerance in control and peptide-treated (0.005 microgram/mouse) animals. In the latter group, however, the level of tolerance was lower than in the control animals. The higher doses (0.05-5.0 micrograms/mouse) inhibited the development of tolerance. Repeated peptide administrations (5, 25, 125 micrograms/animal) did not affect the development of the dependence on alcohol which resulted from combined daily injections of tert-butanol (1.5 g/kg i.p.) and ethanol (3 g/kg i.p.). The severity of withdrawal was quantified via the convulsions induced with different doses of picrotoxin. When the peptide was injected only before the testing of withdrawal, DPLG markedly prolonged the onset of withdrawal signs.

Adenosine is an endogenous neuromodulator with depressant effects on CNS neurons. Adenosine agonists produce biphasic effects on activity, decreases in operant response rate, and anticonvulsant effects. These effects are similar to some of the behavioral effects of ethanol. In addition, it has recently been shown that relative sensitivities to some of the behavioral effects of ethanol and purinergic drugs are similar in inbred strains of mice. These findings have prompted the speculation that ethanol's behavioral effects may be mediated by an agonist action on adenosine-receptive neurons. The present study provided a direct test of this hypothesis with respect to the discriminative stimulus properties of ethanol. In this study, neither the A1 receptor agonist N6-cyclohexyladenosine nor the A2 receptor agonist N6-ethylcarboxamide adenosine produced significant generalization to the ethanol stimulus. In addition, neither the adenosine deaminase inhibitor erythro-9-(2-hydroxy-3-nonyl)-adenine nor the adenosine uptake inhibitor dipyridamole were able to enhance the level of ethanol-appropriate responding seen after a low dose of ethanol. Both caffeine and 8-phenyltheophylline partially but significantly antagonized the stimulus properties of ethanol. However, the doses required to achieve these effects were much higher than those needed to block adenosine receptors. These findings strongly suggest that the discriminative stimulus properties of ethanol are not mediated through an agonist action on adenosine-receptive neurons.

Both aging and chronic ethanol consumption have been correlated with reduced cardiac chronotropic and inotropic function. This study tested the hypothesis that aging potentiates the negative cardiac effects of chronic ethanol consumption. Using isolated tissue techniques we assessed baseline and maximum automaticity and tension development in atria from 4 groups of Fischer-344 rats (young normal, young ethanol, old normal, old ethanol). Baseline and maximum rate was depressed by aging and further depressed by chronic ethanol ingestion. Baseline and maximum tension was depressed only by aging plus chronic ethanol ingestion.

A schedule-induced adjunctive drinking procedure was used to initiate ethanol self-administration in free feeding rats. The rats were first trained on a FI 90-sec schedule with 20% sucrose reinforcement, and then ethanol was made concurrently available on a CRF schedule on a second lever. After 25 concurrent sessions, the sucrose was removed and the ethanol response requirement was brought to FR8. Finally, ethanol concentrations were varied up to 40%. Of 11 rats, 8 responded for sucrose on the FI 90 sec schedule, and 5 of those responded for 40% ethanol at FR8. These results were compared to previous studies using the same procedure in food-restricted rats and other procedures in free feeding rats. Possible explanations for the lower success using schedule induction in nondeprived rats were discussed.