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Query: UMLS:C0278080 (physical dependence)
 1,658 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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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PMID:Ethanol dependence as a determinant of fluid preference. 56 2

The route of alcohol administration used in the experimental study of the role of alcohol in carcinogenesis should mimic the human condition: the p.o. route should, therefore, have major attention. This route appears in concord with epidemiological evidence of alcohol involvement in cancers of the upper digestive tract. The relative advantages of schedule-induced polydipsia, an alcohol solution as the sole fluid source, and an alcohol-containing fluid diet are assessed, as well as the intake of alcohol via the respired air. These routes allow a wide range of daily alcohol doses to be ingested, the largest resulting in continuous intoxication and the development of physical dependence. The equivocal resulta from various already published typical experiments are discussed, indicating the necessity of using a variety of appropriate dosages, dosage routes, and dosage forms in appropriate controls, as well as indicating the necessity of investigating the role of concentration and kind of alcoholic beverage in a variety of strains and species in both sexes and at various ages.
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PMID:Modes of alcohol administration appropriate for the study of the role of alcohol in carcinogenesis. 57 61

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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PMID:Ethanol elimination rates in normal and ethanol dependent animals. 103 70

Schedule-induced ethanol polydipsia regimens were used which produced either one or two daily peaks in blood ethanol levels. After 3 months on these regimens, rats were withdrawn from ethanol and tested for the presence of abstinence signs. No evidence of physical dependence was found, a result which contrasted with the previous finding of a severe withdrawal syndrome when blood ethanol was maintained at a more continuously elevated level prior to withdrawal. It was concluded that, as in the case of barbiturates, the development of physical dependence on ethanol requires more than an episodic peaking of the blood ethanol level once or twice per day.
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PMID:Pattern of daily blood ethanol elevation and the development of physical dependence. 124 46

The technique of chronic schedule-induced drug solution intake was used to determine the possible addiction liability of the short-acting benzodiazepine midazolam. Schedule-induction produces polydipsia over a wide range of fluids as a function of the imposed schedule of food availability. The inducing schedule used presented food pellets automatically once per minute, fixed time (FT) 1-min, for 3 h daily. Two groups of rats, drinking either water or 0.05 mg/ml midazolam solution, were exposed to schedule-induction sessions for approx. 2 months. Then, other FT-values (0, 0.5, 3 and 5 min) were instituted on occasion for single sessions. Each of these 'probe' session determinations was done twice. Although midazolam concentration had been adjusted so that the mean group intakes were equal at FT 1-min, probe values greater than 1 min revealed a greater acceptance of midazolam compared to water. This technique produced session midazolam intakes as great as 25 mg/kg. In the next phase, the entire experiment was repeated except both groups were offered a choice between water and midazolam solution during sessions. Only at FT 0 and FT 5-min was there an indication that midazolam was preferred over water. Two additional groups of animals were exposed to the same schedule-induced polydipsia regimen, drinking water and midazolam solution, respectively. Pre-session administration of doses of Ro 15-1788, CGS 8216 (benzodiazepine antagonists) or midazolam had no effects on either water or midazolam intakes, although the higher dose of midazolam (2 mg/kg, s.c) had a moderately suppressive effect on the non-tolerant water-polydipsic group. All groups were tested on occasion for physical dependence on midazolam with an auditory stimulus as the precipitator and midazolam polydipsic groups were found to have a mild to moderate dependence (clonic seizures, running fits).
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PMID:Midazolam oral self-administration. 316 May 67

Groups of rats drank either a solution of the ultrashort-acting benzodiazepine midazolam or water under schedule-induced polydipsia conditions in chronic, daily, 3-hr sessions. In Experiment 1, the physical dependence status of animals was tested after 9 months by the precipitated withdrawal method using the benzodiazepine-blocking agent Ro 15-1788 and by exposure to a brief audio stimulus at 1.5, 12 and 24 hr following drug withdrawal. Ro 15-1788 failed to produce withdrawal signs, while the audio stimulus plus withdrawal did. In Experiment 2, similar groups were periodically tested for susceptibility to audiogenically-induced seizures at 3, 6, 12, 15, 18, 21, 24 and 26 weeks 90 minutes after their drug or vehicle intake sessions. In the midazolam-drinking group, physical dependence developed at about 12 weeks and increased in severity over the course of the study. Serum measures confirmed that continuous elevation of drug and active metabolite levels are not necessary for the development of physical dependence. A chronic, daily, single elevation of a few hr was sufficient.
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PMID:Development of physical dependence on midazolam by oral self-administration. 360 36

Two groups of rats drinking either 5% ethanol or 0.9% NaCl solution under a fixed-time 1-min schedule of food pellet delivery became polydipsic during daily 3-hr sessions. When both fluids were made available to animals during sessions, strong side preferences typically developed so that neither fluid was preferred in spite of the fact that one group had a mild-to-moderate physical dependence on ethanol. The group that drank 0.9% NaCl solution initially failed to acquire a strong 5% ethanol polydipsia when this became the sole available fluid, and special procedures were required to induce an ethanol polydipsia comparable to that of the other group. Hence, a history of 0.9% NaCl solution polydipsia interfered with the institution of chronic, ethanol overdrinking in this group. Equal ethanol intakes were maintained in the groups when a compound solution consisting of 5% ethanol plus 0.9% NaCl solution was available along with a 5% ethanol choice. Whenever a 0.9% NaCl solution was presented in competition with either 5% ethanol or the compound 5% ethanol plus 0.9% NaCl solution, ethanol intake was reduced. Implications for the prevention and amelioration of human ethanol overdrinking are discussed.
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PMID:Ethanol polydipsic choice: effects of alternative fluid polydipsic history. 381 46

Altered water-electrolyte status resulting from chronic alcohol dependence has been reported, although the nature of any such derangement is controversial. To illuminate this problem, four groups of rats were exposed chronically to schedule-induced polydipsia conditions with a single fluid available: 5% ethanol, 0.9% NaCl solution of 5% ethanol, 0.9% NaCl solution, or distilled water. An ad lib control group was also used. The water-electrolyte status of these groups was evaluated in two ways. First, the diuretic response to hydrochlorothiazide doses (8-12 mg/kg) was measured after 3.5 months of chronic polydipsia. Second, after approximately two additional months of polydipsia, extracellular fluid volume, as well as plasma volume and electrolytes were measured. Both alcohol-intake groups drank approximately 11.5 g ethanol/kg/day over the course of the experiment. Urinary volume response to the diuretic agent did not reveal that chronic ethanol led to either water retention or dehydration, even when extra NaCl intake was imposed chronically (NaCl-EtoH group). Animals that were overdrinking either water or the 0.9% NaCl solution had extracellular fluid volumes that were greater than the NaCl-EtOH-polydipsic group, but they were not significantly larger than ad lib controls. There were no significant differences with respect to serum electrolyte concentration measures among the groups. In conclusion, animals that drank ethanol chronically in a pattern known to produce physical dependence revealed no altered water-electrolyte status when evaluated by acute responses to a diuretic agent, a chronically-imposed extra NaCl load, or body fluid compartment and electrolyte concentration measures.
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PMID:Chronic alcohol dependence and water-electrolyte status. 396 36

A 3-hr schedule-induced ethanol polydipsia regimen was used in rats to elevate blood alcohol concentration to a single intoxicating peak each day. After 3 weeks, and again after 3.5 months, animals were tested for the presence of physical dependence by exposure to a brief auditory stimulus (key shaking) at 7 and 11 hr after ethanol polydipsia. Withdrawal signs were observed only at 11 hr when blood ethanol levels had returned to zero. No such signs were observed when animals were made water polydipsic. While sufficient, continuous elevation of blood ethanol concentration is not necessary for the development of a demonstrable physical dependence. A limited daily ethanol binge was sufficient.
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PMID:Production of physical dependence on ethanol by a short drinking episode each day. 668 78

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.
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PMID:Cross-tolerance to phenobarbital following chronic ethanol polydipsia. 719 69


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