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

As free amino acids in the brain have a role in the development of physical dependence on and tolerance to morphine, and in the mechanism of action of some drugs, the effects of aspartic acid which antagonizes some effects of the single dose of morphine were studied during the development of the physical dependence on morphine and after the withdrawal of morphine. 108 rats were given morphine and aspartic acid in different combinations in drinking water for 30 days. Every tenth day the dose of morphine was increased: At the end of this period some of them in each group continued or began to receive aspartic acid depending on the experimental conditions after the withdrawal of morphine. During the experiments body weight, spontaneous motor activity and analgesic threshold were determined. Aspartic acid prevented the alterations induced by morphine during the development of physical dependence and tolerance. Furthermore the rats that received aspartic acid after the withdrawal showed no body weight loss.
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PMID:Antagonizing effect of aspartic acid on the development of physical dependence on and tolerance to morphine in the rat. 57 36

The effect of electrically induced convulsions was tested on the tolerance to hexobarbital after chronic barbital treatment in male rats. In two experiments barbital was given in the drinking water for more than 20 weeks. The dose was around 200 mg/kg/day. Tolerance was tested with an EEG threshold method where hexobarbital is infused intravenously to obtain a criterion of burst suppression. If on the third abstinent day an electrical convulsion was induced 1 h prior to the threshold determination then the hexobarbital thresholds were reduced compared with barbital-treated animals where no convulsion had been induced (Fig.2). The distribution of hexobarbital threshold doses tended to be biphasic in the barbital-treated animals where a convulsion had been induced. The animals with the most "normal" thresholds in this distribution did not show any increase in threshold on the 24th abstinent day and had a larger mortality during the observation period after the first barbital treatment. Long-term effects of the convulsion thus cannot be excluded in rats if the tolerance on the third abstinent day after a barbital treatment was influenced. No effect of the convulsion was found in untreated controls. The hypothesis that convulsions are means to reduce the changes of physical dependence in the central nervous system was not refuted by the present experiments. A survey of the literature indicates that acetylcholine might be one central nervous transmittor that is involved in these changes.
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PMID:The interaction between electrically induced convulsions and tolerance in the abstinence period after chronic barbital treatments in the rat. 82 78

Individually housed DBA/2J mice were fed a liquid diet in which ethanol supplied 33% of the calories. The level of physical dependence that developed was estimated by scoring convulsions, elicited by handling the mice, after discontinuing the alcohol diet. The severity of the withdrawal reaction increased progressively with duration (5-12 days) of alcohol administration. A 2-day period on the diet produced no withdrawal reaction. Pretreatment of the mice with alcohol in their drinking water slightly increased the subsequent intake of the liquid diet. "Effective" alcohol intake was defined as uninterrupted alcohol consumption above 10 g/kg/day. Withdrawal scores correlated better with effective intake than with total intake under a variety of conditions. We interpret this to mean that brief interruptions in drinking (1 day) may allow the accrued physical dependence to disappear. On the basis of their effective alcohol intake, mice could be assigned to nondependent, moderately dependent or severely dependent groups for further study of the nature of physical dependence.
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PMID:Drinking patterns as predictors of alcohol withdrawal reactions in DBA/2J mice. 98 79

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

Physical dependence on methadone was induced in rats by an initial "forced drinking" procedure and subsequently by i.p. administration of the drug. In a subsequent Experimental Phase of the study the physical dependence of one group was sustained by a "methadone maintenance" treatment, while two other groups were withdrawn from the drug, one gradually and one abruptly. When relapse trials were carried out during a Readdiction Phase it was found that the maintained group voluntarily consumed significantly greater amounts of methadone than did the two withdrawal groups. These groups did not differ between themselves but did in turn ingest significantly more methadone than a control group with no prior exposure to the drug. The characteristic loss of body weight reliably found during withdrawal from morphine was not demonstrated. This may have been due to the unexpected weight loss which occurred during the last stage of the initial Addiction Phase. The dependent variables of amount of methadone solution and the percentage of fluid consumed as methadone solution correlated highly. However the amount of methadone solution ingested was a better indicator of addiction liability as it was not influenced by fluctuations in the amount of water consumed by the animals.
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PMID:Methadone dependence in the rat. 117 53

Reinforcing and physical dependence-producing effects of oral diazepam and triazolam (0.01-1.28 mg/ml) were studied in four non-water-deprived baboons in daily 2-3-h sessions. Drinking initially was food-induced, but subsequently it was maintained for greater than year without the inducing procedures; drug intake greater than 10 mg/kg per session was attained. Triazolam and diazepam reinforcement (compared to vehicle) was concluded for only one baboon for each drug under a single-spout procedure and for two baboons for each drug under a two-spout procedure. However, all baboons showed ethanol reinforcement under a two-spout procedure. When a lever-pressing requirement was imposed for each drink (one-spout procedure), ethanol maintained requirements of 128 or 256 responses/drink, and volume of ethanol consumed was greater than vehicle. Neither benzodiazepine maintained lever pressing better than vehicle at any response requirement and drinking was suppressed by requirements of 1-32. Physical dependence to triazolam and diazepam developed after approximately 1 month of daily ingestion, evidenced by a precipitated withdrawal syndrome after injection of the benzodiazepine antagonist flumazenil. A mild spontaneous withdrawal syndrome occurred after substitution of vehicle for triazolam or diazepam. These data indicate a clear dissociation between the reinforcing and physical dependence-producing effects of triazolam and diazepam.
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PMID:Oral self-administration of triazolam, diazepam and ethanol in the baboon: drug reinforcement and benzodiazepine physical dependence. 152 81

Thiofentanil is a synthetic analgesic with pharmacological effects similar to etorphine hydrochloride (M99). The aim of the present study was to assess its analgesic and immobilization effects and to evaluate its dependence potential in comparison with morphine. The median analgesic dose (AD50) was measured by hot plate method in mice. The median paralytic dose (PD50), as an indicator of immobilization, was tested in rats, rabbits, dogs and monkeys. Results showed that the analgesic potency of this drug was 3260 times that of morphine, 22 times that of fentanyl and 1.5 times that of M99 and the immobilization effect was 2-3 times that of M99. Results from jumping test in mice and physical dependence-producing test in rats (the drug was dissolved in drinking water) showed that thiofentanil possessed physical dependence liability weaker than morphine. Physical dependence was not observed in rats with intravenous injection of one dose each h over a period of 72 h, and also in monkey with 20-week drug medication. The LD50 of thiofentanil was also determined in mice, rats, rabbits, dogs and monkeys in comparison with M99. Results suggest that it should be valuable to develop thiofentanil as an analgesic for clinical use.
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PMID:[Experimental study on the principal effects and dependence potential of thiofentanil]. 168 5

When given a two-bottle choice between gradually increasing morphine concentrations (in 0.2% saccharin) and plain tap water, C57BL/6J mice consumed almost 90% of their daily fluid intake from the morphine-saccharin bottle, while the DBA/2J strain, in contrast, consumed 13% or less from the morphine-saccharin solution. The C57BL/6J strain consistently consumed mean daily doses of morphine sulfate in excess of 200 mg/kg, which was sufficient to induce an easily discernable withdrawal syndrome upon removal of the morphine solution, either with or without naloxone challenge. Hypothermia, tremor, wet dog shakes, jumping, and diarrhea were prominent withdrawal signs. In separate experiments, the saccharin was removed from the morphine-containing bottle, yet the C57BL/6J mice continued to prefer the morphine solution over tap water. In complete contrast to the above, mice of the DBA/2J strain rejected the morphine-saccharin solution at the lowest concentration employed, and at no time did their mean daily morphine dose exceed 20 mg/kg. Thus, morphine-saccharin preference is strongly genetically determined, and a high degree of physical dependence can result in the morphine-preferring strain. Palatability differences appear not to be the predominant explanation for these differences in morphine-saccharin consumption.
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PMID:Physical dependence induced by the voluntary consumption of morphine in inbred mice. 232 Jun 38

Although p.o. self-administration of morphine is a reliable and convenient means of inducing physical dependence, its effects on brain monoamine metabolism have not been determined. Accordingly, in the present experiment young Wistar rats drank increasing concentrations (0.1-0.5 mg/ml) of morphine in water, or water alone, for 37 days. Half the rats in each group were challenged with morphine (10 mg/kg s.c.) when 27 to 29 hr withdrawn, and half with saline. Rats were sacrificed 2 hr postinjection. Seven brain regions were analyzed for noradrenaline (NA), dopamine (DA), or 5-hydroxytryptamine (5-HT), and their respective metabolites. In all cases in which a comparison could be made with prior work utilizing repeated injections to produce dependence, the p.o. regimen produced the same effects. Thus, the mode of administration does not seem to modify the response of monoaminergic neurons to chronic morphine. In withdrawal, NA turnover increased but DA and 5-HT turnovers decreased. Acute morphine accelerated the turnover of all three monoamines. The NA response was attenuated in some brain regions of withdrawn rats, indicating the development of tolerance to the turnover-enhancing effect of acute morphine in noradrenergic neurons. In contrast, the effect of acute morphine on cerebral 5-HT turnover was not altered, and its effect on cerebral DA turnover was enhanced in withdrawn rats. Our results suggest that there are fundamental differences among the three monoaminergic systems in their capacities for adapting to chronic morphine treatment.
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PMID:Changes in brain monoamine metabolism during withdrawal from chronic oral self-administration of morphine and in response to a morphine challenge in the withdrawn state. 246 63

The ability of temazepam and midazolam to substitute for pentobarbital and thus maintain the physical dependence state was used to assess the potential dependence liability of these two benzodiazepine compounds. Male Sprague-Dawley rats, weighing 175-200 g and having ad lib access to food and water, were determined to be dependent on pentobarbital following 12 days of continuous, intraperitoneal infusion of pentobarbital using an escalating drug infusion schedule. On day 13 (substitution phase) the pentobarbital was replaced with either temazepam, midazolam or vehicle and the rats were infused for an additional 24 hours. This was followed on Day 14 (withdrawal phase) by a 24 hr saline infusion period. Rats were observed for changes in overt behavior and alterations of body weight during both Day 13 and Day 14. Preliminary potency estimation studies had indicated that both drugs were more potent and longer acting than was pentobarbital. Temazepam, in doses of 32.5, 65 and 130 mg/kg/24 hr, was demonstrated to substitute for pentobarbital and provided dose-dependent suppression of overt behavioral signs indicative of withdrawal. Temazepam also suppressed the weight loss typically observed during withdrawal. Substitution of saline for temazepam resulted in an increased incidence of withdrawal signs and an approximate 10% decline in body weight. Midazolam, in doses of 60 and 120 mg/kg/24 hr, also substituted for pentobarbital and suppressed both overt behavior and weight loss. Following saline substitution on Day 14, a mild withdrawal syndrome was evident although body weight was noted to remain near control values.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Substitution of temazepam and midazolam in pentobarbital-dependent rats. 257 97


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