Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0278080 (physical dependence)
 1,658 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Continuing our characterization of the ethanol inhalation model for chronic ethanol administration, we have now measured the magnitude and time course of functional tolerance, for comparison with physical dependence and with biochemical and biophysical studies of tissues taken from alcohol-treated mice. Ethanol was administered to mice by inhalation for 1 to 9 days, using pyrazole to maintain continuously elevated blood ethanol levels. At different times after termination of the ethanol administration, a test dose of ethanol was administered by injection and the sensitivity of the mice was assessed by measuring the brain concentration of ethanol at which the animals lost their balance on a horizontal rod. Tolerance, tested at 6 hr after withdrawal and expressed as a ratio of brain ethanol concentrations of mice that had been chronically treated with ethanol and their controls, was measurable after only 1 day of ethanol treatment and increased further in experiments of 3 and 6 days duration, but did not continue to increment during 9 days of alcohol inhalation. The tolerance disappeared rapidly after withdrawal; it was maximal at the earliest test; 2 hr after withdrawal, but decayed progressively and was no longer appreciable 30 hr after withdrawal. The method is suitable for accurate measurement of ethanol sensitivity, even when residual alcohol remains from the chronic treatment.
 ...
PMID:Time course of functional tolerance produced in mice by inhalation of ethanol. 668 83

Physical dependence on ethanol was produced in four rhesus monkeys by IV ethanol administration every 8 h. Ethanol was administered on each occasion until the eyeblink reflex was lost. Evidence of physical dependence development, in the form of tremoring 8 h after an infusion, appeared on day 8 of chronic administration. Abrupt cessation of ethanol administration following 16 days of chronic administration was accompanied by moderate to severe tremoring, retching, vomiting, and one or more convulsions. Peak withdrawal occurred between 12 and 32 h after abrupt discontinuation of ethanol administration, and decreased over a period of 64-204 h. Ethanol dependence was then reinstated. Once every 3-4 days, ethanol was withheld for 16 h. Withdrawal signs were scored for the first 12 h of this period, and then a test dose of ethanol, phenobarbital, or baclofen was administered. Withdrawal or intoxication signs were scored over the next 4 h, at which time ethanol administration was resumed. Both ethanol and phenobarbital suppressed ethanol withdrawal signs in a dose-related manner, and produced dose-related intoxication. Baclofen was largely ineffective in reducing withdrawal-induced tremors, although it was capable of producing sedation of a different type than that produced by phenobarbitol and ethanol.
 ...
PMID:The effects of ethanol, phenobarbital, and baclofen on ethanol withdrawal in the rhesus monkey. 677 81

A new subcutaneous form of ethanol exposure in rats is described. The Sustained Ethanol Release Tube (SERT) for rats is similar to an earlier device reported for mice, except that only one refill per day is required. This device, plus an intragastric loading dose for initially raising blood ethanol levels (BEL), is capable of maintaining high BEL for greater than 12 hours. Supplementation of SERT-released ethanol with a Sustacal chocolate-flavored diet with 37% of total energy as ethanol produces high, stable BEL for indefinite periods. Maintenance of such BEL for 9 days is sufficient to cause dramatic withdrawal signs when ethanol exposure is stopped. The method is useful as a model for conveniently and quickly producing physical dependence to ethanol in rats.
 ...
PMID:Subcutaneous silastic implants: maintenance of high blood ethanol levels in rats drinking a liquid diet. 720 46

Alcohol is one of the most popular drugs of abuse in our society, and alcoholism is an important cause of absenteeism at work and a major health and social problem. Ethanol induces a number of effects, such as disinhibition, a feeling of general well-being, tolerance and physical dependence. Since there are no specific receptors with which ethanol interacts, it has been proposed that ethanol exerts its effects by altering the activity of a number of neuronal and neuroendocrine systems. Studies have indicated that alcohol influences the activity of the dopaminergic, serotonergic and opioidergic systems. The implication of the endogenous opioid system in mediating some of the effects of ethanol is indicated by the observations that some of the behavioral and pharmacological effects of ethanol are similar to those of the opiates. Indeed, injections of small amounts of morphine increased ethanol consumption, while the administration of naltrexone decreased ethanol consumption among rats and other experimental animals, in a number of experimental paradigms, suggesting that endogenous opioids may play an important role in controlling voluntary ethanol consumption. This paper reviews studies of the effects of ethanol on the activity of the endogenous opioid system and on the importance of endogenous opioids in controlling alcohol consumption.
 ...
PMID:Endogenous opioids and excessive alcohol consumption. 769 May 85

Modulation of alpha 2-adrenergic and opioid neurotransmission may contribute to ethanol intoxication, tolerance, and physical dependence. We showed previously that ethanol increased the expression of functional delta-opioid receptors in NG108-15 cells (Charness, M. E., Querimit, L. A., and Diamond, I. (1986) J. Biol. Chem. 261, 3164-3169). Here we report that long-term (2 days) treatment of NG108-15 cells with ethanol increased the binding of the alpha 2-adrenergic receptor (alpha 2AR) antagonist [3H]rauwolscine and the muscarinic acetylcholine receptor (mAChR) antagonist [3H]quinuclidinyl benzilate by 2.8- and 1.4-fold, respectively. Increased receptor expression was associated with a proportionate increase in the potency of oxymetazoline and carbachol in inhibiting cAMP accumulation. Ethanol did not change the expression of G alpha i2 and reduced levels of G alpha s. Pertussis toxin pretreatment did not prevent the ethanol-induced increase in alpha 2AR, mAChR, and delta-opioid receptor expression. Ethanol caused a large (3.6-fold), dose-dependent increase in the abundance of alpha 2BAR mRNA (rat cDNA probe RNG, 4.1-kb transcript). Ethanol-induced increases in alpha 2BAR and alpha 2CAR (rat probe RG10, 2.5-kb transcript) mRNAs were first detected after 6 h of exposure to 100 mM ethanol, became maximal after 24 h, and persisted for up to 5 days. In contrast, ethanol caused only a small (1.3-fold) increase in the abundance of hm4 mAChR mRNA and did not change levels of G alpha i2 and G alpha s mRNAs. Our data indicate that clinically attainable concentrations of ethanol regulate alpha 2AR gene expression within the time frame of a single session of drinking.
 ...
PMID:Ethanol differentially increases alpha 2-adrenergic and muscarinic acetylcholine receptor gene expression in NG108-15 cells. 822 69

1,1,1-Trichloroethane (TCE), a widely used and abused solvent, was investigated for its ability to produce physical dependence in mice. Cessation of 4 days of continuous inhalation of TCE (500-4000 ppm) resulted in a withdrawal syndrome characterized by handling-induced convulsions and increased susceptibility to pentylenetetrazol-induced convulsions. The severity of withdrawal convulsions was diminished by 30 to 60 min of reexposure to 2000 to 4000 ppm TCE or to the vapor of another widely used and abused solvent, toluene (1000-2000 ppm). Ethanol (1-2 g/kg), midazolam (0.3-1 mg/kg) and pentobarbital (30 mg/kg) were also effective in decreasing the withdrawal severity; however, chlorpromazine (3 mg/kg) and phenytoin (30 mg/kg) were without effects. These data suggest that TCE has the ability to produce physical dependence of the central nervous system depressant drug type. Taken together with other evidence for similarities in the pharmacological and behavioral effects of TCE and depressant drugs of abuse, these data support the hypothesis that the basis for TCE abuse may be its ability to produce ethanol- and depressant drug-like effects.
 ...
PMID:Inhaled 1,1,1-trichloroethane-produced physical dependence in mice: effects of drugs and vapors on withdrawal. 843 20

Chronic administration of ethanol in animals leads to CNS tolerance and physical dependence. Subsequent withdrawal of ethanol causes hyperexcitability which is thought to be related to increased sensitivity of N-methyl-D-aspartic acid (NMDA) receptors. The purpose of this study was to investigate sensitivity to NMDA in ethanol-treated animals by detecting damage after intrahippocampal injection of NMDA. Choline acetyltransferase (ChAT) and glutamate decarboxylase (GAD) specific activity was used as markers of cholinergic and gamma-aminobutyric acid neurons, respectively. Ethanol-dependent animals were more liable to die following intrahippocampal injection of either 120 or 240 nmol of NMDA. There was a significantly greater decrease in hippocampal GAD but not ChAT specific activity in the surviving animals. These data support the hypothesis that ethanol dependence is associated with increased sensitivity to NMDA which may be responsible for excitotoxic brain damage and death.
 ...
PMID:Increased sensitivity of the hippocampus in ethanol-dependent rats to toxic effect of N-methyl-D-aspartic acid in vivo. 846 3

The 2-[14C]deoxyglucose method was used to examine the effects of chronic, voluntary ethanol consumption on rates of local cerebral glucose utilization (LCGU). LCGU was measured in male Long-Evans rats immediately following the completion of a 60-min schedule-induced polydipsia drinking session. Three groups of animals were examined: animals with a history of ethanol consumption that received ethanol on the test day (ethanol-ethanol), animals with a similar ethanol history that were presented with water on the test day (ethanol-water), and a control group that received water throughout the experiment (water-water). Ethanol consumption on the test day resulted in a highly discrete pattern of metabolic changes, with significant decreases in glucose utilization in the hippocampal complex, habenula, anterior ventral thalamus, and mammillary bodies, whereas increases were observed in the nucleus accumbens and locus coeruleus. Rates of LCGU in the ethanol-water group were increased throughout all regions of the central nervous system examined, indicating that the long-term consumption of moderate ethanol doses that do not produce physical dependence can cause significant changes in functional brain activity.
 ...
PMID:Metabolic mapping of the effects of chronic voluntary ethanol consumption in rats. 874 4

The effect of acutely applied ethanol and the impact of chronic ethanol treatment, sufficient to induce tolerance and physical dependence, on N-methyl-D-aspartate (NMDA) receptor function were studied in acutely isolated neurons from the medial septum/diagonal band (MS/DB) of adult rats using whole cell, patch-clamp electrophysiology. There was a small positive correlation for capacitance and current amplitude activated by 100 microM NMDA for all groups. Also, cell membrane capacitance was significantly smaller for Ethanol Dependent (approximately 80-84%) than either Naive or Control cells. Therefore NMDA-activated responses were normalized for capacitance (current density, pA/pF) across all three groups. NMDA-activated (30-1000 microM) responses were significantly larger in cells from Control and Ethanol Dependent rats relative to those from Naives. In addition, estimated maximal responses were significantly larger for Ethanol Dependent cells, compared to either Control or Naive, respectively, while EC50s and slopes were not significantly different. Acute 60 mM ethanol significantly inhibited responses to 100 microM NMDA in all three groups, however, mean ethanol inhibition was 12-25% smaller after ethanol dependence. There was no evidence of acute tolerance to ethanol inhibition for any group, but examination of patterns of inhibition for individual neurons showed a few cells were resistant to ethanol or exhibited progressive loss of ethanol inhibition. These results suggest that NMDA receptor function in acutely isolated MS/DB neurons is increased following in vivo chronic ethanol treatment, and shows resistance to acute ethanol inhibition suggesting NMDA receptor-mediated cellular tolerance.
 ...
PMID:Ethanol inhibition of NMDA currents in acutely dissociated medial septum/diagonal band neurons from ethanol dependent rats. 951 48

The direct impact of ethanol on native, non-NMDA glutamate receptors was examined in acutely isolated MS/DB neurons from rat. The impact of ethanol functional tolerance and physical dependence on non-NMDA receptor function was also determined. Non-NMDA receptors were defined pharmacologically as predominantly the AMPA subtype, because both AMPA- or kainate-activated currents were blocked by GYKI 52466, a selective AMPA receptor antagonist. The relative magnitude of potentiation of AMPA-activated currents by 10 or 100 microM cyclothiazide was consistent with recombinant AMPA flop-subtype receptors. Finally, the selective kainate receptor agonist, SYM 8021, induced little current in MS/DB neurons. AMPA receptor currents when activated by kainate were sensitive to ethanol, showing inhibition of approximately 5 - 50% when 10 - 300 mM ethanol and kainate were briefly co-applied (3 s). Ethanol (100 mM) also inhibited both the initial transient peak and sustained currents activated by AMPA. Inhibition was sustained during continuous ethanol superfusions of 5 min, suggesting a lack of acute tolerance to ethanol-induced AMPA receptor blockade. Rapid application of 3 - 3000 microM kainate activated concentration-dependent currents in MS/DB neurons from Control and Ethanol Dependent animals that were not significantly different. Also, direct ethanol inhibition (300 mM) of kainate-activated currents was not reduced by ethanol dependence, suggesting a lack of functional tolerance. These results suggest that native AMPA receptors on MS/DB neurons are inhibited by pharmacologically-relevant concentrations of ethanol. However, these receptors, unlike NMDA receptors, do not undergo adaptation with sustained ethanol exposure sufficient to induce physical dependence. British Journal of Pharmacology (2000) 129, 87 - 94
 ...
PMID:Sustained ethanol inhibition of native AMPA receptors on medial septum/diagonal band (MS/DB) neurons. 1069 6


<< Previous 1 2 3 4 Next >>