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

The homeostat hypothesis of drug addiction states that tolerance and physical dependence may both represent adaptive processes, the body's responses to drugs that change the internal milieu. This conceptual framework inextricably links physical dependence with functional tolerance. Dependence may arise by multiple mechanisms, so that different signs, such as body temperature or CNS excitability, may show different degrees of dependence or may have different time courses. Tolerance may be similarly diverse. It is difficult to test whether tolerance and dependence have the same time course because it is hard to find exactly equivalent signs for such a test. The discrepant data from different laboratories on the rate of recovery from physical dependence may be due to the use of different withdrawal signs as indices. Dissociation of tolerance and dependence has been reported in mice treated with 6-hydroxydopamine, where dependence develops without evidence of tolerance. Conversely, tolerance without expression of dependence is seen in experiments on membranes and synapses in vitro. Changes in lipid composition of cell membranes may explain some kinds of tolerance.
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PMID:Physical dependence on ethanol: its relation to tolerance. 51 Jan 74

There is a need to define the field of drug addiction from both the theoretical and the practical point of view, but any attempt to do so encounters difficulties that are inherent in the many types of approach as well as in the polymorphism of drug addiction. The difficulties are also due to the present day consumption of pills which is very high both among members of our "square" society and in the marginal fringes, and occurs in and outside the field of drug addiction proper -- the guide being here the progressive increase of doses. The modes of use are not sufficient to determine the presence of drug addiction: the drug substance must have a psychism-oriented tropism; the increase in the dose of a non-psychotropic product is therefore a matter of hypochondria and not of drug addiction. The means of administering a drug also occupies a privileged place, in so far as the intravenous method suffices alone to label non-medical use as drug addiction. It is the hallucinogens that, despite the absence of physical dependence, most frequently pose the question of the definition of drug addiction, in view of the ritual dimension and the transgressive significance of the absorption of these products, even at relatively moderate doses, and hallucinogens pose this question all the more since their use emerges from a sub-cultural environment that produces typical drug addiction, namely intravenous heroin addiction. The latter does not raise the question of definition, but is used as the basis for a drug addiction referential system.
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PMID:[Identification in drug addiction]. 123 94

Physical dependence on narcotics is induced in laboratory animals by intermittent parenteral administration (2 approximately 3 times daily). However, inducing of dependence on pethidine has been unsuccessful using the parenteral method. Recently, it has been reported that physical dependence on pethidine can be induced by continuous infusion methods (5.6). In the present experiment, pethidine was administered to rats (n=5 approximately 6) by ingestion of pethidine-admixed food preparations (0.5 approximately 4.0 mg/g of feed). The results indicated that (a) when rats are allowed free access to two food preparations (0.5 mg/g vs. 1 mg/g of food) for 7 weeks, spontaneous intake ratios of food (1 mg/g of food) gradually increased from 15% to 30% after 3 weeks. (b) Abrupt withdrawal for 48 hr after a 10 day administration period (2 mg/g of food on day 1 approximately 3 and 4 mg/g of food on day 4 approximately 10) resulted in a loss of body weight in the next 24 hr, and the prewithdrawal level of body weight was recovered in 48 hr. (c) The time course of body weight and food intake during the first 24 hr withdrawal period demonstrated the characteristic pattern of abstinence syndrome of pethidine, viz. early onset (12 approximately 13 hr) and rapid recovery (within 48 hr), as compared to morphine withdrawal. (d) Suppression of pethidine abstinence of both a single injection of morphine (10 mg/kg, s.c.) and substitution for morphine-admixed food was also realized. (e) When levallorphan (5 mg/kg, s.c.) was administered to both pethidine and morphine dependence rats, the maximal decrease in body weight was less than that in morphine dependent rats. These data indicate that pethidine possesses about one fifth the dependence liability of morphine and the maximal abstinence syndrome appears within 24 hr after withdrawal. Conclusively, application of a drug-admixed food preparation in drug dependence tests in rats has proven to be a useful method, particularly in the case of pethidine-like drugs which rapidly disappear from the blood.
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PMID:[A study on drug dependence using fast acting drugs]. 123 48

The technical term 'drug dependence' was officially adopted by WHO's Expert Committee on Addiction in 1964. Until this, to describe a state of dependence, terms such as 'poisoning', 'habit', 'ism', and 'addiction' had been used from time to time. Until the 1950's, investigators were mainly focussed on the phenomena of physical dependence. However, once the concept of psychic dependence had been introduced, behavioral and neuropharmacological studies on the modes of drug action that produce psychic dependence were activated and have progressed in the last two decades, and among the points clarified by these studies are the following: 1. The critical drug properties that produce psychic dependence are those of rewarding subjective and reinforcing effects of drugs but these effects are not the properties that produce physical dependence, although the development of physical dependence on particular drugs such as opiates may substantially enhance craving for the drugs. 2. The mesolimbic and mesocortical dopamine systems in the brain and also the N. Accumbens play a primary or at least a partial role in producing the subjective and reinforcing effects of major dependence-producing drugs such as cocaine, opiates, barbiturates, benzodiazepines, and ethanol. 3. Many drugs such as naltrexone, methadone, and some dopamine antagonists and serotonin reuptake inhibitors or antagonists were found to be effective in the pharmacotherapy of the dependence on opiates, cocaine, or ethanol.
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PMID:[Overview of the progress in drug dependence studies--mainly focussing on psychic dependence]. 142

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

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

The treatment of severe pain requires the use of potent opioid analgesic medications. Many patients with opioid sensitive pain are being undermedicated. This results in increased morbidity and needless suffering. The most important reason for this undertreatment is the fear of addiction engendered by opioids, a fear that is greatly out of proportion to the real risk. The risk of addiction is greatly overestimated in part because many people do not understand the distinctions between drug abuse and drug addiction, on the one hand, and physical dependence and tolerance, on the other. Dependence and tolerance are virtually inevitable outcomes of long-term opioid use, but they are neither sufficient to cause addiction nor the equivalent of it. Indeed, the evidence shows that only a tiny fraction of patients treated with opioids become addicted. There is little risk of addiction for those patients receiving properly administered opioids for pain.
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PMID:Perspectives on the medical use of drugs of abuse. 196 89

The lifelong nature of panic disorder and the development of effective new treatments have focused attention on long-term use of antipanic medications, particularly benzodiazepines and their possibly addictive nature. Benzodiazepines are generally safe and effective. An understanding of the distinction between chemical dependence and physical dependence places problems involved in the use and discontinuation of benzodiazepines into perspective. Patients with a dual diagnosis of panic disorder and chemical dependence are at risk of addiction. Others may develop physical dependence but are able to discontinue benzodiazepine treatment when panic symptoms subside. The approach to benzodiazepine use and discontinuation should be different for patients with chemical dependence as opposed to patients with physical dependence. A four-step approach to discontinuation that is applicable to both groups is offered.
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PMID:Thinking about stopping treatment for panic disorder. 225 76

The significance of beta-endorphin for drug dependence was explored by measuring the levels of beta-endorphin-immunoreactivity (beta E-IR) in plasma and parts of pituitary and brain of rats self-administering heroin or cocaine as compared to animals offered saline. Rats that had intravenously self-administrated heroin for 5 consecutive daily sessions of 6 h, and were decapitated immediately after the last session, showed a decreased concentration of beta E-IR in the anterior lobe (AL) of the pituitary while rats that had taken cocaine showed a decreased concentration of beta E-IR in the septum. Rats that had self-administrated heroin or cocaine and were decapitated 18 h after the last session, showed an increased concentration of beta E-IR in plasma and decreased concentrations in the AL of the pituitary and in specific areas of the brain limbic system, i.e. nucleus accumbens, septum, hippocampus and rostral striatum. The finding that self-administration of both the opiate heroin, inducing psychic and physical dependence, and the non-opiate cocaine, inducing psychic but not physical dependence, is accompanied by similar changes in beta E-IR concentrations particularly in limbic brain structures, and that these effects are present 18 h but not immediately after the last session, suggests that beta E and related peptides in limbic brain regions may represent a neurochemical correlate for psychic dependence on drugs.
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PMID:Beta-endorphin in brain limbic structures as neurochemical correlate of psychic dependence on drugs. 252 16

Research with laboratory animals has provided several insights into the nature of cocaine abuse and addiction. First, the nature of drug addiction has been reevaluated and the emphasis has shifted from physical dependence to compulsive drug-taking behavior. Second, animal studies suggest that cocaine is at least as addictive as heroin and possibly even more addictive. Third, cocaine is potentially more dangerous than heroin as evidenced by the higher fatality rate seen in laboratory animals given unlimited access to these drugs. Fourth, the neural basis of cocaine reinforcement has been identified and involves an enhancement of dopaminergic neurotransmission in the ventral tegmental dopamine system. Other addictive drugs (e.g., opiates) may also derive at least part of their reinforcing impact by pharmacologically activating this reward system. Fifth, although the biological consequences of repeated cocaine self-administration on central nervous system functioning are poorly understood, preliminary findings suggest that intravenous cocaine self-administration may decrease neural functioning in this brain reward system. This has important clinical implications because diminished functioning of an important brain reward system may significantly contribute to relapse into cocaine addiction. These and other findings from experimentation with laboratory animals suggest new considerations for the etiology and treatment of drug addiction.
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PMID:New perspectives on cocaine addiction: recent findings from animal research. 268 64


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