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

Physical dependence liability of chlorphenesin carbamate (CPC) was studied in parallel with phenobarbital-Na (PB). Beagle dogs were used and the overall duration of the experiment was 85 days, i.e. the first dosing period was 42 dyas (6 weeks) in which drugs were repeatedly administered orally once daily, followed by a withdrawal period (7 days), the second dosing period was continued from the 50th-78th day in which the form and schedule of drug administration was as in the first dosing period. The last 79th to 85th days were used for substitution experiments. In both dosing periods, PB but not CPC showed signs of tolerance formation. Severe withdrawal syndrome was observed in PB administered dogs whereas there were no changes of behavior observed in CPC-dogs by withdrawal and substitution procedures, respectively. CPC apparently does not have a physical dependence liability.
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PMID:[Studies on the physical dependence liability of chlorphenesin carbamate (author's transl)]. 56 35

The intraventricular administration of 6-hydroxydopamine before chronic ethanol exposure prevented the development of tolerance to the hypnotic and hypothermic effects of ethanol as well as cross-tolerance to barbiturates. The injection of 6-hydroxydopamine depleted brain norepinephrine but had little effect on levels of dopamine and serotonin. Although mice pretreated with 6-hydroxydopamine did not develop tolerance to ethanol, they exhibited signs of physical dependence after chronic treatment with ethanol. If 6-hydroxydopamine was administered after tolerance to ethanol was established, the destruction of noradrenergic neurons had little effect in disrupting the tolerance. Noradrenergic systems may be necessary for the "consolidation" but not the expression of tolerance.
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PMID:The effects of 6-hydroxydopamine on tolerance to and dependence on ethanol. 56 43

Male Golden Hamsters drank large amounts of ethanol with food and water freely available, when ethanol was presented in water at concentrations of 10-40% (w/v). Although the hamsters consumed an average of 13.8 g/kg/day of ethanol for 3 months, no withdrawal signs were observed during 4 days without ethanol, nor were withdrawal signs observed during withdrawal after 4 more months of ethanol consumption. Although the Golden Hamster consumes large amounts of ethanol without the need for food or water deprivation, the Golden Hamsters may have limited usefulness as a model of physical dependence.
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PMID:Failure of signs of physical dependence to develop in hamsters after prolonged consumption of large doses of ethanol. 56 65

Infant rats, treated intracisternally with 6-hydroxydopamine or 5,7-dihydroxytryptamine, alone or in combination with desmethylimipramine or pargyline, at 5 to 7 days of age, had significant specific depletions of brain norepinephrine, dopamine, both of these amines, or serotonin at 2.5 months of age. Despite apparent long-term depletions of brain biogenic amines, susceptibility to audiogenically-induced seizures following chronic ethanol withdrawal in these animals was similar to that of controls. Amine-depleted rats also displayed spontaneous withdrawal-induced tremors, spastic motor activity and irritability. The interpretation of these preliminary findings with regard to the proposed role of the biogenic amines in the development of physical dependence on ethanol is discussed.
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PMID:Effects of 6-hydroxydopamine or 5,7-dihydroxy-tryptamine on the development of physical dependence on ethanol. 56 50

Influence of morphine on the fine structure of mitochondria in the cells of zona fasciculata of the adrenal cortex in mice in which a morphine pellet was subcutaneously implanted was studied using electron microscope. (1) Transformation of the mitochondrial structure, i.e. swelling, formation of lamellar or concentric circular cristae and decrease of electron density of the mitochondrial matrix, was observed 12 hr after implantation, and changes reached a maximum state at 48 hr. These transformations, however, disappeared wihtin 4 days. (2) On the 4th day after implantation, removal the pellet again produced transformation of the mitochondria with withdrawal symptoms, and a normal state was reverted to 72 hr later. Levallorphan challenge produced similar changes. (3) Injection of morphine into mice after removal of the pellet prevented the appearance of mitochondrial transformation. From the results obtained it may be concluded that there are correlations between the transformation of the mitochondria and physical dependence on morphine in mice.
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PMID:[Studies on the physical dependence liability of analgesics. 5th report: Electron microscopic studies on the ultrastructural transformation of mitochondria in the cells of zona fasciculata of the adrenal cortex in morphine pellet implanted mice (author's transl)]. 56 4

ICR male mice each receiving a 16 mg barbital pellet implanted subcutaneously for three days developed about 40 percent tolerance to barbital and more than 50 percent tolerance to pentobarbital as measured by sleeping time. The development of physical dependence in these mice was demonstrated by an increased sensitivity to convulsions with pentylenetetrazol. The concentration of barbital rose to high levels in the subcortex and the cerebellum during the time between the implantation of the pellet and the loss of the righting reflex and distributed uniformly thereafter. After a challenge dose of the drug, higher barbital concentrations were found in these two areas as well as in the pons-medulla at 30 minutes and in all areas at the time of the loss of righting reflex, in withdrawn mice. The latter finding would indicate an increase in threshold for barbital anesthesia. The mechanisms of the higher uptake in the brain of withdrawn mice are discussed.
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PMID:Regional distribution of barbital in the brain of mice during the development of tolerance and physical dependence. 56 25

Morphine dependence in mice is produced in a two day test. The effects of (1) ethanol, (2) pyrazole, (3) ethanol with pyrazole, and (4) pentobarbital are observed and recorded on the naloxone precipitated escape response in morphine dependent mice. Ethanol suppresses the escape response in doses of 2.0 and 3.0 g/kg which produce mean blood ethanol concentrations of 1.88 and 3.28 mg/ml, respectively. When a pyrazole regimen is employed with morphine dependent mice, ethanol reduces or abolishes the naloxone precipitated escape response at doses of 1.0, 2.0 and 3.0 mg/kg. The corresponding mean blood ethanol concentrations are 1.14, 2,82 and 3.74 mg/ml, respectively. When pentobarbital (20 and 30 mg/kg) is given to morphine dependent mice, jumping bevarior is prevented following naloxone injection. Since narcotic antagonists such as naloxone may be employed in studying the phenomenon of physical dependence on ethanol based on the hypothesis of a relationship between endogenous opiates and ethanol dependence, it is essential to verify that blood ethanol concentrations are low enough so that ethanol will not interfere with the effects of naloxone in ethanol dependent animals.
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PMID:The effects of ethanol and pentobarbital on the naloxone precipitated escape response in morphine dependent mice. 56 45

1. A slow release emulsion of naloxone (naloxone SR) was administered subcutaneously to rats in an attempt to induce physical dependence of the morphine type. 2. Naltrexone (2.5 mg/kg), injected i.p., failed to elicit an abstinence syndrome in rats treated with 75, 100 or 150 mg/kg naloxone SR for 24, 48, or 72 h. 3. Naloxone SR had no effect on the whole brain levels of noradrenaline, dopamine, homovanillic acid or serotonin. 4. Naloxone SR caused an apparent dose-related increase in the brain levels of 5-hydroxyindoleacetic acid. 5. These results show that while naloxone does not induce physical dependence of the morphine type, it may, like morphine, increase the brain serotonin turnover rate. 6. It is proposed that the increase in brain serotonin turnover rate may not be causally related to physical dependence on morphine-like drugs but may be a property of drugs containing the basic opiate molecular structure.
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PMID:Dissociation of increased 5-hydroxyindoleacetic acid levels and physical dependence: the effects of naloxone. 56 13

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

This paper describes methods of analysing temporal patterns of alcohol consumption by mice over time-courses of days or hours. Records of daily alcohol intake can be used to identify brief periods when the mice sobered up. These one-day 'breaks' apparently allow the previously acquired level of physical dependence to decay. Effective alcohol intake, calculated by taking account of breaks, is a good indicator of physical dependence. More detailed time studies show the circadian rhythm of intake and of blood alcohol levels. To analyse our records of alcohol consumption over successive 8-hour periods, we fitted the data to cosine curves. These curves show the amplitude of the intake rhythm, which in turn determines the stability of blood alcohol levels. The highest and most stable blood alcohol levels were obtained by administering alcohol in a liquid diet to individually-housed mice.
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PMID:Temporal patterns of voluntary alcohol intake. 56 68


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