uvr Genes function differently in repair of acetylaminofluorene and aminofluorene DNA adducts.
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Biomedical subjects
Publications and source records attributed to M Tang.
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Rats exposed to daily 3-hr intermittent food delivery sessions (binging) chronically ingested excessive amounts of either H2O or 5% EtOH (mean 7.1 g/kg/3-hr). Withdrawing the intermittency of the feeding schedule once every 10 days (single-ration probe session) resulted in reduction of fluid intakes (both H2O and EtOH) to the level of animals always given daily single-ration sessions. This complete dependence of elevated fluid intake levels on the intermittent feeding schedule was unaffected by either the number of probes previously administered (0 to 11) or the duration the feeding schedule was maintained before introduction of the first probe session (29 or 109 days). The results of the probe sessions demonstrated that a history of ethanol overindulgence was not a sufficient condition for the maintenance of overdrinking. Continued overindulgence required the continued presence of the original inducing conditions. Ethanol-polydipsic animals exposed to periodic probe sessions also developed a slow rise in binge session intake. No such increase was observed in the water-polydipsic animals.
Using contingent food pellet delivery, rats were trained on a discriminative motor control task requiring that a force transducer be held steadily within a force band. Motor performance following pre-task doses of phenobarbital (40, 60 or 80 mg/kg) both before and after 4 months fo chronic ethanol polydipsia (mean intake = 11.1 g/kg/kay)indicated the development of cross-tolerance from ethanol to phenobarbital. Days on which saline control injections were given in place of phenobarbital injections (on injection days ethanol was withdrawn 5 hr pre-injection) revealed the development of a mild physical dependence on ethanol at this level of ethanol polydipsia. Chronic ethanol polydipsia did not alter the time course of phenobarbital elimination from the serum, indicating that the cross-tolerance probably was due to central nervous system changes.
Rats exposed to a daily 3-hr session of intermittent food delivery ingested physical-dependent levels of a 1 mg/ml sodium phenobarbital solution. This chronic, voluntary, high level of session phenobarbital intake had no effect on 21-hr home cage barbiturate preference. Substitution of water for phenobarbital during the session after 7.5 weeks precipitated various spontaneous withdrawal signs in some of the animals by the 24th hr of drug withdrawal but no change was found in home-cage barbiturate preference at any time. Physical dependence alone does not seem to play a crucial role in the maintenance of drug intake behavior.
An animal model of human alcoholism is presented in which animals maintain chronic overdrinking to the extent that they develop severe physical dependence. They can be induced to overdrink ethanol in situations where an alternative fluid is present as well, so that the overindulgence is elective. The environmental conditions that produce this result also can induce the overingestion of other substances, aggression, and hyperactivity. It would appear, then, that many kinds of seemingly excessive, maladaptive behavior in animals and humans can have similar environmental sources. Alcoholism may be viewed within a context of environmental conditions that can produce a variety of excesses.
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Rats drinking a low concentration (2.5%) of ethanol in a chronic, schedule-induced polydipsia situation failed to show withdrawal signs as measured by a discriminative motor control task. When the concentration was raised to 5% ethanol, withdrawal signs were evident, confirming a previous study.
A procedure for determining barbiturate levels in micro-samples is described. The method takes advantage of a newly available, sensitive nitrogen-phosphorus detector thereby permitting a simplified analytic procedure.
Serum barbiturate levels were tracked for several hours in food deprived rats given 40, 60 or 80 mg/kg (SC) of either phenobarbital or barbital. All 3 phenobarbital doses produced peak serum drug levels at 1.5 hr postinjection. Serum barbital concentrations peaked 3 hr after both 60 and 80 mg/kg barbital doses while the 40 mg/kg dose produced a stable low drug level throughout the 4 postinjection hours. For both barbiturates administered, 40 mg/kg doses produced lower serum drug levels than either 60 or 80 mg/kg. The differences in serum drug concentrations between the latter two dose levels were inconsistent over time.
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Rats made dependent on ethanol by a schedule-induced polydipsia procedure preferred 5% ethanol to an increasing concentration of dextrose solution to a greater extent than animals on a non-dependent, non-polydipsic procedure which allowed an equivalent opportunity to drink ethanol, confirming a previous study. Two corresponding groups of animals drinking isotonic (0.9%) NaCl rather than 5% ethanol behaved similarly to the latter group, changing to a dextrose preference at a lower dextrose concentration than the ethanol polydipsic group. Therefore, neither the intermittent food regimen (polydipsia-generating procedure) in itself, nor a history of isotonic saline polydipsia biased fluid preference against dextrose solution choices. The enhanced preference for ethanol over dextrose solutions shown by the ethanol polydipsic group can be attributed to physical dependence rather than regiment produced artifacts.
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Ethanol elimination rates were determined in rats using an intravenous route of ethanol administration after several experimental manipulations. Twenty-four hr food deprivation resulted in a 30% reduction to 35 mg/100ml blood/hr in elimination rate from a non-deprived rate of 50 mg/100 ml blood/hr. After 2 months of ethanol drinking (5% v/v), 24 hr starvation resulted in only a 10% reduction in elimination rate (45 mg/100 ml blood/hr), and did not increase the non-food-deprived rate (49.2 mg/100 ml blood/hr) over that obtained in the above animals' drinking water rather than 5% ethanol. Animals which chronically overdrank ethanol or water for 3 months on a schedule-induced polydipsia procedure, known to result in ethanol physical dependence, showed a decreased rate of ethanol elimination (37.9 mg/100 ml blood/hr for water drinkers) in the non-food-deprived condition. By providing 750 mg of liver powder daily as a food supplement in the ethanol overdrinking regimen, the ethanol elimination rate remained at a rate comparable to the normal animal (48.4 mg/100 ml blood/hr).
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