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

Disputing the concept of "psychic dependence", the authors review six motivations to use addictive drugs, four of which pertain to the moment of assumption of the habit, and two of which, identifiable with physical and psychic dependence, depend on breaking of the habit. While physical dependence is linked to withdrawal syndrome, psychic dependence, in the authors' opinion, is related to a longstanding previous state of true of masked endogenous depression (in this case it would be well termed "neuropsychological dependence"), and the drug taking is only a maladaptive self-medication. This thesis is substantiated by the literature reporting, in chronic drug addicts, the use of the whole series of antidepressants (i.e. tricyclics, doxepine, lithium, etc.) with noticeable therapeutical success. In accordance with other reports and with personal experience, the authors assign great importance to the drugs acting, directly or indirectly, on GABA, i.e. L-glutamine, piracetam, and, particularly, N-dipropylacetic acid.
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PMID:Psychic dependence? A different formulation of the problem with a view to the reorientation of therapy for chronic drug addiction. 2 89

Disputing the concept of "psychic dependence", the Authors review six motivations to use addictive drugs, four of which pertain to the moment to assume the habit, although the latter two, which are identifiable with physical and psychic dependence, depend on te breaking the habit. While physical dependence is linked to withdrawal syndrome, psychic dependence, on the Author's opinion, is related to a long-standing previous state of true or masked endogenous depression (in this case it would be well termed as "neuropsychological dependence"), and the drug taking is only a maladaptive self-medication. This thesis is substantiated by the literature, reporting, in chronic drug addicts the use of the whole series of antidepressants (i.e. tricyclics, doxepine, lithium, etc.), with noticeable therapeutical success. According with other reports and with personal experience, the Authors maintain a great importance to drugs acting, directly or not, on GABA, i.e. l-glutamine, piracetam, and, particularly, N-dipropilacetic acid.
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PMID:[Psychological dependence? A possible different formulation of the problem for a therapeutic rearrangement in chronic drug addictions]. 33 Nov 41

Chronic administration of ethanol to mice by inhalation for 10 days produced physical dependence demonstrated by a characteristic syndrome of withdrawal. Free amino acid concentrations in whole brain were measured at intervals during the induction of dependence and during withdrawal. During the induction of dependence there was an initial increase in brain glycine, a sustained increase in brain tyrosine and reductions in brain GABA and proline. Serine and isoleucine concentrations were consistently reduced during the induction of dependence, but this change was not significant (P less than 0-05) at any single time interval studied. After the withdrawal of ethanol only the reductions in GABA and proline persisted during the withdrawal syndrome. In addition to these changes an increase in brain glycine concentration was observed during the ethanol withdrawal syndrome. In an attempt to discriminate between the immediate, metabolic effects of ethanol on central amino acid concentrations and those changes associated with the induction of ethanol dependence, the results were compared with those obtained when mice were exposed to a high concentration of ethanol vapour for 3 h. Although this produced similar blood ethanol concentrations, no evidence of physical dependence was observed. The changes in central amino acid concentrations differed from those seen during the induction of dependence in that no change in isoleucine concentration occurred, and that the reduced concentrations of GABA and proline very rapidly reverted to control values when ethanol was removed. The possible role of central amino acids in ethanol dependence is discussed.
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PMID:Concentrations of free amino acids in brains of mice during the induction of physical dependence on ethanol and during the ethanol withdrawal syndrome. 55 41

Central nervous system depressants, e.g. barbiturates, alcohol and benzodiazepines, have a wide spectrum of activity in humans and animals. Evidence accumulated suggests that some of the pharmacological actions exerted by these agents may be mediated through GABA system by mimicking GABAergic transmission. This proceeding briefly summarizes the evidence presented in our previous review (Yu S and Ho Ik: Alcohol 7: 261, 1990) as to how the GABA system plays a part in the barbiturate actions and the development of tolerance to and physical dependence on barbiturates. The comparisons of the effects of alcohol, barbiturates and benzodiazepines at different steps of GABA synapse are also discussed. Furthermore, the results which have been reported in the literature are inconsistent. This may be due to differences in (a) animal models used; (b) brain regions used; (c) protocols (dose, duration, form and route of administration, etc.) used in treating animals and/or (d) techniques (pharmacological, biochemical, physiological, etc.) used.
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PMID:Effects of barbiturates on GABA system: comparison to alcohol and benzodiazepines. 168 71

In previous studies, development of functional tolerance to the anticonvulsant effect of clonazepam and physical dependence on the drug have been demonstrated. In the present study, dogs were treated for 6 weeks with clonazepam 0.5 mg/kg b.i.d. Under methohexital anesthesia, cerebrospinal fluid samples were taken before treatment, at 3 days (acute effect), 4 and 5 weeks (tolerance) after the start of treatment, 2 and 8 days after withdrawal and 5 weeks after the end of treatment as another control. The following transmitters or metabolites were determined: HVA, VMA, 5-HIAA, GABA, PGE2, TXB2 and 6-keto PGF1 alpha. 5-HIAA levels showed a significant rise, indicating an increased activity of the serotonergic system in the brain during development both of tolerance and withdrawal. Dopaminergic activity was not altered during treatment, but was increased after cessation of treatment, as indicated by a significant increase in HVA concentrations.
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PMID:Metabolism of central neurotransmitters during development of tolerance to the anticonvulsant effect of clonazepam and of physical dependence on the drug in dogs. 170 Jun 84

The recent investigations on biochemical and biophysical mechanisms of ethanol in acute intoxication, tolerance and physical dependence suggest that the cell membrane, intracellular metabolism and central neurotransmitters are involved. In acute intoxication ethanol increases the "fluidity" of the cell membrane and stimulates the central gabergic system. In alcoholics, the body adapts, and in the presence of ethanol, the cell membrane becomes more "rigid" and the gabergic system hypoactive. When alcohol intake is discontinued the hypoactivity of the gabergic system is unmasked and it is manifested as withdrawal syndrome. The alcohol intake compensates for the clinical symptoms of decreased gabergic activity and thereby continuously prevent the onset of withdrawal symptoms. On the other hand, intact central noradrenergic and 5-hydroxytryptaminergic systems as well as the neuropeptide vasopressin maintain the tolerance. After withdrawal syndrome, membrane alterations and the state of diminished gabergic activity gradually return to normal. This period of slow recuperation corresponds to the subacute withdrawal syndrome. In this period, there is a continuous desire for alcohol intake. Further, alcoholics, in this situation, are very vulnerable with feelings of insecurity, fragility and isolation. All these factors additionally induce a latent desire for ethanol. It follows then that a stimulation of decreased gabergic activity is a new approach in drug therapy of alcoholism. One of these new stimulants is acamprosate. The new substance is a structural analogue of GABA and acts as an agonist on gabergic receptors. Therefore, acamprosate improves the central gabergic activity. Alcoholics treated with acamprosate stated that they no longer felt a desire for alcohol intake. In this way, acamprosate maintains the abstinence for several months during the post-withdrawal phase.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Modern drug therapy in alcoholism]. 180 68

Central nervous system depressants, e.g., barbiturates, alcohol and benzodiazepines, have a wide spectrum of activity in humans and animals. Evidence accumulated suggests that some of the pharmacological actions exerted by these agents may be mediated through GABA system by mimicking GABAergic transmission. This review attempts to summarize the evidence available as to how the GABA system plays a part in the barbiturate actions and the development of tolerance to and physical dependence on barbiturates. The comparisons of the effects of alcohol, barbiturates and benzodiazepines at different steps of GABA synapse are also presented. Furthermore, the results which have been reported in the literature are inconsistent. This may be due to differences in: (a) animal models used; (b) brain regions used; (c) protocols (dose, duration, form and route of administration, etc.) used in treating animals and/or (d) techniques (pharmacological, biochemical, physiological, etc.) used.
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PMID:Effects of acute barbiturate administration, tolerance and dependence on brain GABA system: comparison to alcohol and benzodiazepines. 197 Apr 80

The effect of in vitro and in vivo administration of ethanol on the binding of 35S-t-butyl-bicyclophosphorothionate (35S-TBPS) to cortical brain membranes of C57Bl mice was investigated using KCl (100 mM) containing assay media. The in vitro addition of ethanol produced a dose-dependent inhibition of basal 35S-TBPS binding. In the presence of chloride ions, GABA and pentobarbital had a biphasic action (stimulation followed by inhibition) on 35S-TBPS binding, whereas diazepam only stimulated the binding. Ethanol reduced the stimulatory effects of GABA and pentobarbital in a dose-dependent manner, but had no effect on the enhancement of 35S-TBPS binding produced by diazepam. 35S-TBPS binding to cortical brain membranes was inhibited by the putative Cl- channel blocking agent DIDS. This inhibitory action of DIDS was significantly, and dose-dependently reduced by ethanol (greater than or equal to 100 mM ethanol). Chronic ethanol ingestion in vivo, which produced tolerance to and physical dependence on ethanol in the animals, did not alter the stimulatory and inhibitory effects of GABA and pentobarbital on 35S-TBPS binding. The enhancement of 35S-TBPS binding produced by diazepam was slightly, but significantly, enhanced in brain membranes from animals which had undergone 24 hours of ethanol withdrawal. Chronic ethanol treatment did not change the potency of picrotoxin and of the peripheral BDZ-receptor ligand RO 5-4864 to competitively inhibit 35S-TBPS binding. Our results suggest that in vitro addition of ethanol alters the activity of the GABA/benzodiazepine (BDZ) receptor complex.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effect of ethanol on 35S-TBPS binding to mouse brain membranes in the presence of chloride. 262 67

Chronic ethanol treatment which produced intoxication and physical dependence in rats, produced an increase in the specific binding of ethanol antagonist [3H]RO15-4513 in rat brain cerebral cortex and cerebellum, but not in hippocampus and striatum. The increase in both the regions was due to an increase in the number (Bmax) of receptor sites. These results suggest that the RO15-4513 binding sites on the oligomeric GABA receptor complex are altered following chronic ethanol administration, and support the notion of a unique role of RO15-4513 as an ethanol antagonist.
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PMID:Chronic ethanol administration increases the binding of the benzodiazepine inverse agonist and alcohol antagonist [3H]RO15-4513 in rat brain. 285 Sep 26

GABA-stimulated 36Cl- influx was used to investigate regional differences in response to chronic diazepam treatment by comparing cortical and cerebellar tissue from rats chronically treated with diazepam for 3 weeks. Using a treatment protocol which has previously been shown to produce behavioral tolerance and physical dependence, cortical membrane preparations from chronic diazepam-treated rats were found to exhibit a decreased responsiveness to the stimulation of 36Cl- influx by GABA and a corresponding decrease in the ability of flunitrazepam to enhance GABA-stimulated 36Cl-influx. This decrease in sensitivity to flunitrazepam, however, appears to reflect the underlying decrease in sensitivity to GABA. In contrast, in membrane vesicles prepared from cerebella of chronic diazepam-treated rats, there was no measurable effect on GABA-stimulated 36Cl--influx or on the enhancement of GABA-stimulated 36Cl- influx by flunitrazepam. These results support the suggestion that there is a regionally specific reduction in GABA/benzodiazepine receptor function following chronic benzodiazepine treatment.
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PMID:Chronic diazepam treatment produces regionally specific changes in GABA-stimulated chloride influx. 292 Jul 72


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