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

A method for the chronical administration of morphine by the oral route is discussed and compared with the production of physical dependence to morphine by injection. The method recommends the administration of Morphine HCl dissolved in a 45% sucrose syrup and given orally for 4 weeks. The initial concentration of morphine in the syrup was 1 mg/ml and was increased weekly up to 4 mg/ml at the end of the experiment. This procedure rendered the animals physically dependent on morphine as observed by drug withdrawal, when abstinence symptoms were easily identified.
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PMID:The production of morphine tolerance and physical dependence by the oral route in the rat. A comparative study. 10 Aug 15

The i.v. pentylenetetrazol seizure threshold was increased by 2.5 mg/kg and decreased by 15 mg/kg of a single (+)-amphetamine dose. After 7 consecutive days of amphetamine administration, tolerance developed to the decrease but not to the increase in seizure threshold. At 12--48 h after the last dose of 2.5 mg/kg seizure threshold was decreased, and at 36--48 h after the last dose of 15 mg/kg seizure threshold was increased. After acute and chronic administration of (+)-amphetamine (2.5 mg/kg) endogenous concentrations of whole brain dopamine (DA) were increased and returned to normal levels during the withdrawal period (12--48 h); endogenous norepinephrine (NE) levels were unchanged by acute and chronic drug treatment and during withdrawal. The rates of DA and NE synthesis were increased by chronic amphetamine administration at 24--48 h after drug withdrawal. An acute dose of (+)-amphetamine (15 mg/kg) decreased endogenous levels of DA and NE; normal levels of DA were detected with chronic drug treatment and during withdrawal, with NE remaining slightly depressed. The rates of synthesis of DA and NE were increased by acute and chronic amphetamine treatment and returned to normal 24--48 h after withdrawal. The rebound reversal in seizure threshold after (+)-amphetamine withdrawal suggests an abstinence syndrome that may be interpreted as evidence for the development of physical dependence to (+)-amphetamine after chronic drug administration.
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PMID:The effects of chronic administration and withdrawal of (+)-amphetamine on seizure threshold and endogenous catecholamine concentrations and their rates of biosynthesis in mice. 40 70

To analyze the drug ingestion patterns of rats in the course of dependence development while on the drug-admixed food (DAF) method, an automatic food intake measuring apparatus was developed. Rats were put on morphine-admixed food, and the food ingestion patterns were recorded with the apparatus in the course of dependence development, during drug withdrawal and at the time of challenge with levallorphan. The naive rats ate the regular diet intermittently at night, and the eating time of morphine-treated rats was longer than that of naive rats. The treated rats also exhibited a frequent eating behavior after 4--5 days on the morphine treatment. During morphine withdrawal, the animal gradually ate the regular diet at about 1-hour intervals, even after evolvement of abstinence signs. When the morphine-dependent rats were given levallorphan, they neither ate nor approached to the food for the first 2--3 hours, but after this time, showed abrupt increases in these activities. Thus, the drug intake pattern of rats in the course of morphine dependence development suggests a correlation between the stage of development of physical dependence and the stage when the animals frequently eat the drug-admixed food.
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PMID:Eating pattern of morphine dependent rats. 57 97

The effect of three dosage schedules on the expression of a withdrawal syndrome indicative of physical dependence on pentobarbital was determined in male Sprague-Dawley rats. Rats were prepared with an intraperitoneal cannula and were continuously infused with either saline (control) or pentobarbital sodium, using an escalating drug dosage schedule, for either 5 (PB-5), 13 (PB-13) or 20 (PB-20) days. Final doses reached were 500 mg/kg/day (PB-5) and 1000 mg/kg/day (PB-13). PB-20 rats reached 1000 mg/kg/day on day 13 and were maintained at this dose for an additional 7 days. Body weight, water consumption and assessment of CNS depression were obtained daily. Following the last day of pentobarbital infusion all rats were infused with saline for a 72-hour drug-free period. Water consumption, body weight and assessment of overt behavioral signs indicative of a drug withdrawal syndrome were obtained at specific times during the drug-free period. PB-5 rats showed little evidence of withdrawal while PB-20 rats demonstrated the greatest degree of withdrawal. Peak withdrawal scores were observed to be 1, 3.8 and 5 for PB-5, PB-13, and PB-20, respectively. Withdrawal scores for group PB-13 and PB-20 were found to be significantly greater than either control or PB-5 but were not significantly different from each other. Body weight for PB-13 and PB-20 mice declined slightly (nonsignificant) during the drug-free period while a significant decrease (40% decline) in water consumption was demonstrated by 24 hours of this period.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Intensity of the withdrawal syndrome varies with duration of pentobarbital administration. 262 53

There was no overt evidence of the development of physical dependence, as shown by a decrease in the body weight of rats following the abrupt withdrawal of dextropropoxyphene after two weeks administration. The ambulation and rearing scores in the 'open field' apparatus were increased after chronic, but not acute drug administration and returned to control values two days following drug withdrawal. GABA turnover, determined from the rise in GABA concentrations following GABA-transaminase inhibition, was reduced in the frontal and amygdaloid cortex after acute and chronic drug administration; a compensatory rise in GABA turnover in the amygdaloid cortex occurred two days after drug withdrawal. Na+, K+, ATP'ase activity, determined in a synaptosomal fraction from the mid-brain and hippocampus, was decreased in the latter region only during drug administration; a compensatory increase in the activity of this enzyme was found two days after drug withdrawal. These results support the view that chronically administered dextropropoxyphene may cause changes in inhibitory transmission and central neurotransmitter transport.
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PMID:Acute and chronic effects of dextropropoxyphene on behaviour and central inhibitory neurotransmission in the rat. 299 72

Flupirtine maleate is a centrally acting analgesic with a novel chemical structure and pharmacological profile. Because of its central mechanism(s) of action, flupirtine maleate was studied for physical dependence liability and abuse potential using the following four laboratory animal models: (1) mouse jumping test--jumping behaviour after narcotic antagonist challenge; (2) Hosoya test in rats--body weight reduction after drug withdrawal or narcotic antagonist challenge; (3) tolerance in mice--reduced analgesic activity after repeated dosing; and (4) self-administration in addicted Rhesus monkeys. Unlike the narcotic analgesic agents morphine and codeine, flupirtine maleate did not display evidence of physical dependence liability or abuse potential as measured by jumping behaviour in mice or body weight reduction in rats following repeated oral administration. Doses equal to or in excess of its analgesic dose were given for up to five weeks in these studies. No tolerance developed to the analgesic activity of flupirtine maleate in mice or rats dosed for up to 19 consecutive days. Finally, in morphine-dependent Rhesus monkeys, there was no difference in the rate of self-administration of flupirtine maleate when compared to the saline vehicle. Therefore, these results clearly show that flupirtine maleate, in animals, is without abuse potential and physical dependence liability.
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PMID:Abuse potential and physical dependence liability studies with flupirtine maleate in laboratory animals. 344 27

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

Compulsive hypnosedative drug use is commonly associated with the development of tolerance and physical dependence. As most data are derived from human or animal experiments, electroclinical correlations in the clinical field are rather scarce. The informative value of the EEG features registered in 22 patients presenting minor and/or major signs of a clinical hypnosedative drug withdrawal syndrome are discussed. The electroclinical correlations are investigated and the physiopathogenesis of both clinical and EEG dysfunction are related to the neurochemical theory of dependence and withdrawal. It is suggested that the drug withdrawal syndrome represents a transient unbalanced metabolic state at the neuronal cellular level, which may be included among the causes of metabolic encephalopathies. The severity of this encephalopathy and the moment at which it occurs depend on both exogenous and personal factors.
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PMID:The EEG in hypnosedative drug withdrawal and dependence. 652 64

Morphine preference and tendency to relapse to morphine tolerance and dependence were studied in rats which were previously made morphine dependent. Tolerance to, and physical dependence on, morphine were initially produced by administration of increasing concentrations of morphine sulphate in 5% sucrose solution for 3 weeks. A test for drinking preference was performed 4 days after the rats had been successfully detoxified and showed no significant signs of morphine dependence. It was found that, while control animals drank only negligible amounts of morphine solution, previously morphine-dependent rats consumed significantly larger volumes of morphine solution and had recurrence of morphine tolerance and dependence. The present findings show that chronic administration of morphine in drinking fluid produces tolerance and physical dependence as well as addiction in rats; the latter definition is exemplified by these animals having a high tendency to relapse after successful drug withdrawal.
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PMID:Morphine preference in rats previously morphine dependent. 653 22

Attempts have been made to examine the relationship between urinary excretion of sex-dependent low molecular weight proteins found only in male rats (LMWP) and morphine physical dependence. Chronic administration of morphine produced a dose-related decrease in urinary LMWP excretion, which was correlated to the intensity of withdrawal signs including body weight loss and abnormal behaviors recognized after naloxone challenge. Furthermore, a statistically high correlation was obtained between the decrease in urinary LMWP excretion and the loss of body weight precipitated by naloxone challenge. LMWP was identified immunologically in the livers, kidneys, and sera using an antibody against purified LMWP. The serum level of LMWP was increased rapidly following bilateral nephrectomy. After chronic treatment with morphine, the LMWP content in the livers, kidneys, and sera were decreased. These findings indicate that the decrease in urinary LMWP excretion induced by chronic administration of morphine can be a useful parameter to assess the development of physical dependence on narcotics on the peripheral level without requiring drug withdrawal and naloxone challenge. This decrease in urinary LMWP may be caused by the inhibition of LMWP synthesis in the liver.
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PMID:A new approach for assessment of narcotic physical dependence using urinary sex-dependent low molecular weight proteins in male rats. 668 90


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