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

The (+)-amphetamine circling rate of rats with unilateral 6-OHDA lesions in the striatum was recorded. Morphine tablets were implanted subcutaneously for chronic treatment. In the morphine-dependent animal the circling rate to amphetamine given 4 days after morphine was first implanted was depressed but after withdrawal with naloxone a day later the rate increased, returning to normal after 21 days. Barbiturate physical dependence was induced by adding increasing amounts of barbitone to the drinking water of lesioned rats over four weeks after which the amphetamine circling response was depressed and remained so after the barbituate was withdrawn. Ethanol tolerance was induced by adding ethanol to the drinking water of lesioned rats for four weeks. Neither the induction of tolerance over this period nor ethanol withdrawal had any effect on the circling response to amphetamine. The change in the response of striatal dopamine neurons to amphetamine that occurs after chronic morphine treatment, cannot be produced by chronic treatment with either barbitone or ethanol. The neurochemical bases of barbiturate and ethanol tolerance are different from morphine tolerance.
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PMID:Effect of tolerance to morphine, ethanol and barbiturate on amphetamine circling in rats with a striatal dopamine lesion. 2 10

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

Intravenous infusions were used to produce physical dependence upon ethanol in rats. The procedure proved to be safe, rapid, and reliable. Ethanol (30% v/v) was administered over a 7-day period. The mean daily dose ranged from 10--14 g/kg/day. Control rats were exposed to a comparable procedure except that saline, rather than ethanol, was infused. All ethanol treated rats that survived the intoxication period (n = 11) showed signs of physical dependence (moderate to severe, n = 8; mild, n = 3) following ethanol withdrawal. Saline treated rats (n = 8) did not show any of these symptoms. The most reliable ethanol withdrawal signs observed were: spontaneous seizure (n = 7), audiogenic seizure (n = 7), tremors (n = 6), tail stiffening (n = 10) and body rigidity (n = 9). These symptoms were analyzed in terms of their hour of onset and hour of maximum intensity following ethanol withdrawal. Application of the intravenous method for the study of ethanol self-administration is discussed.
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PMID:Induction of physical dependence upon ethanol in rats using intravenous infusion. 56 3

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

This paper reports findings relative to a simple, rapid and reproducible technique for the induction of physical dependence upon ethanol in the rat. The dependence was induced by intragastric intubation of 20% (w/v) ethanol solutions at 9-15 g/kg in 3-5 fractional doses daily for 4 days, maintaining blood ethanol concentrations above a threshold level sufficient to sustain observable sedation throughout the entire period of intubation. Two phases were distinguished during the withdrawal period: 1. Prodromal detoxication, characterized by a spectrum of signs and responses of diminishing severity, related to the decline in blood ethanol concentrations (mg/dl): death, greater than 640; coma, 780-460; loss of righting reflex, 640-400; ataxia 3-1, 570-250; sedation 340-190; neutrality, 220-130; 2. Ethanol dependence, characterized by a spectrum of withdrawal signs and reactions of progressively increasing severity as blood ehtanol concentration approached 100 mg/dl: hyperactivity, tremors, akinesia, spastic rigidity, and induced and spontaneous convulsions. A rapid sucession of two diverse clusters of signs and reactions represents a reversal of the central nervous system function from the extremes of ethanol intoxication (CNS depression) to the extremes of ethanol dependence (CNS hyperexcitability) during the withdrawal period. Both extremes may terminate in death.
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PMID:Induction of physical dependence upon ethanol and the associated behavioral changes in rats. 123 14

1. Ethanol-induced sleep time was significantly longer in F344 than LEW rats. However, there is no difference in barbital-induced sleep time between F344 and LEW. 2. Development of tolerance to ethanol-induced motor impairment was slightly faster in F344 than in LEW rats. While, LEW rats more easily developed tolerance to the impairment by barbital in comparison with F344 rats. 3. F344 and LEW rats were chronically treated with liquid diet containing ethanol or with barbital-admixed food. After the termination of ethanol and barbital treatments, various withdrawal signs occurred in F344 rats, including tremor and convulsions, whereas LEW rats showed no convulsions. Withdrawal scores of ethanol and barbital were significantly higher in F344 than in LEW rats. 4. These results suggest that strain differences in physical dependence on ethanol and barbital may be mainly influenced by the susceptibility to ethanol and the development of tolerance to barbital, respectively.
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PMID:Susceptibility to, tolerance to, and physical dependence on ethanol and barbital in two inbred strains of rats. 159 18

The additive drugs alcohol, morphine, cocaine, and amphetamine are each associated with the development of tolerance and physical dependence. Changes in gene expression occur in cell culture and in vivo with the administration of these centrally-acting drugs. This article reviews those experiments that have studied drug-induced alterations in gene transcription. Ethanol has diverse effects on the amounts of messenger RNA molecules within the central nervous system. Ion channels, neuropeptides, membrane receptors, and immediate early genes represent several regulated mRNAs. The effects are selective, however, as many other specific products are not altered. Evidence for a genetic predisposition to ethanol use reinforces the importance of the genotype. Opioids, cocaine, and amphetamine also affect gene transcription. Messenger RNAs studied have included many of those demonstrated to be altered by alcohol use. Interestingly, use of any of these drugs alters the expression of immediate early genes. These genes may represent an initial step in the pathway that leads to drug addiction. The composite of drug-induced changes in gene expression results in the cellular responses of tolerance and dependence. The characterization of these changes should provide a better understanding of the molecular mechanisms of drug addiction.
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PMID:The molecular biology of addictive drugs. 172 3

The functional state of GABAA receptors during physical dependence on ethanol was evaluated in two ways. First, the ability of ethanol dependence to change the convulsant potency of GABAA antagonists microinjected into the inferior colliculus was examined. A second approach evaluated the effects of ethanol dependence on the ability of muscimol or pentobarbital to stimulate chloride uptake in rat brain vesicles. In the studies examining changes in convulsant potency, bilateral microinfusions of GABAA antagonists, bicuculline methiodide and picrotoxinin, as well as the excitatory amino acid agonist, kainic acid (used as a positive control) induced similar dose-related increases in the frequency of wild-running seizures. Ethanol dependence did not significantly change susceptibility to wild-running seizure induction by an of the convulsants, although susceptibility to the more severe, clonic seizures was significantly increased for each convulsant. This suggested that the receptor-blocking effects of GABAA antagonists responsible for inducing wild-running seizures were not selectively increased by ethanol dependence, but that spread of seizure activity responsible for clonic seizures following the initiation of wild running was generally increased. Finally, in studies examining changes in GABAA receptor-mediated chloride uptake, both muscimol and pentobarbital were found to induce concentration-dependent increases in chloride uptake in rat brain vesicles. However, responses to these drugs were not reduced by ethanol dependence suggesting that a generalized adaptive decrease in GABAA receptor function was unlikely. Together these results do not provide support for the hypothesis that the GABAA receptor-chloride channel complex is down-regulated during the development of physical dependence on ethanol.
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PMID:Effect of ethanol dependence on GABAA antagonist-induced seizures and agonist-stimulated chloride uptake. 178 22

In a rat model of alcoholism, different stages of the development towards a drug addiction can be discriminated. During the phase of "controlled" intake, drug consumption is reversibly modified by the social situation (housing conditions) and the individual's social role (in particular his dominance rank). In Wistar rats, this period lasts about half a year. During the next few months, the consumption of ethanol rises without a concomitant loss of its behavioral effects. After an abstinence period of nine months, the rats maintain a high preference for alcohol which cannot be suppressed by adulteration with (unpleasantly tasting) quinine. Ethanol-taking behavior can no longer be modified by external stimuli or by dominance rank. This irreversible state is called "behavioral dependence." It is drug-specific (i.e., other drugs like diazepam cannot substitute the alcohol) and not related to physical dependence. In behaviorally dependent rats, the effects of ethanol are altered; very low doses tranquillize the rats, higher ones stimulate them.
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PMID:An ethopharmacological approach to the development of drug addiction. 179 14

Ethanol physical dependence can be viewed as a state of latent hyperexcitability in brain which is exposed on withdrawal of the drug. This hyperexcitability may reflect an increased sensitivity to Ca2+ of central neurones. Dihydropyridine (DHP) binding sites which represent a subtype of neuronal Ca2+-channel, are increased in brains from ethanol-dependent rats as are functional effects of the DHP Ca2+-channel activator, BAYK8644. These effects are reversed by DHP Ca2+ inhibitors, which also prevent the ethanol physical withdrawal syndrome. These results suggest that an increase in DHP-sensitive Ca2+-channels on central neurons may represent the molecular basis for ethanol physical dependence.
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PMID:Increased dihydropyridine-sensitive calcium channels in rat brain may underlie ethanol physical dependence. 243 83


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