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

The development of drug taking from controlled intake to drug addiction was studied by means of an animal model. Outbred rats had continuous free access to water and drinking fluids containing different concentrations of a drug for 7-9 months. After an abstinence period of 4-9 months, the drug was offered again (retest). Previous ethological classification of each rat and changes of housing conditions were used to study the modifiability of drug taking. With ethanol and the mu-agonistic opiate etonitazene, two stages followed each other. Controlled drug intake was adjusted to situational and individual variables. Social isolation of the rats raised the intake of ethanol and opiate. Dominant rats took less drugs than subordinate ones, but, in contrast to the latter, increased drug consumption after social disturbances. The adjustment of drug taking to social variables, was accompanied by changes in the dopaminergic and GABAA-ergic neurotransmission and by altered responses to acute drug administrations. Further, place preference, associated with reinforcing stimuli was modulated by subchronic sensitization/desensitization of dopaminergic transmission. Controlled drug intake lasted for 6-8 months, after which a spontaneous increase of drug consumption was found which latently continued during abstinence periods of 1 month. In the retest after abstinence, drug intake of these rats was strongly increased compared with both their previous consumption and that of drug-naive controls. Since drug taking could no longer be modulated by gustatory, environmental or individual factors (loss of control), it was considered as addictive. Addiction appeared to be specific to the kind of the drug. It persisted for the rest of the rat's life. After long periods of abstinence, ethanol-addicted rats revealed a completely altered pattern of response to self-administered alcohol compared with controlled drinkers. Their dopaminergic D1-transmission was irreversibly altered. Drug addiction only developed when the rat had free choice between water and drug-containing solutions. Long-term forced administration of ethanol or opiate, only led to physical dependence bot not to addiction. Some applications of the animal model are discussed, concerning the assessment of risk factors, the intake of drug combinations, residual neurochemical changes and concepts of treatment.
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PMID:From controlled drug intake to loss of control: the irreversible development of drug addiction in the rat. 851 31

Previous studies have shown that chronic, forced exposure to opiates produces specific biochemical adaptations in the ventral tegmental area (VTA) and nucleus accumbens (NAc). The functional consequences of these adaptations have been hypothesized to contribute to certain motivational aspects of drug addiction. In this study, the possibility that similar adaptations could occur in response to intermittent heroin self-administration was tested by comparing homogenates of VTA and NAc from rats self-administering heroin, rats receiving yoked injections of heroin, and rats receiving yoked injections of saline (controls). Tyrosine hydroxylase (TH) immunoreactivity was increased (31-38%) in the VTA and decreased (11%) in the NAc of heroin-exposed rats relative to controls. Heroin exposure also increased cAMP-dependent protein kinase (PKA) activity in both particulate (19-27%) and soluble (17-20%) fractions of the NAc, and decreased (16-17%) the level of Gi alpha immunoreactivity in this brain region. In contrast, no significant biochemical changes were found in the substantia nigra or caudate-putamen, indicating a selective effect on the mesolimbic dopamine system. Overall, adaptations in the VTA and NAc of heroin-exposed rats were similar to, but generally smaller in magnitude than, adaptations produced by chronic morphine administration. However, in contrast to morphine-treated animals, heroin-exposed animals failed to display overt signs of opiate physical dependence, suggesting that adaptations in motivational systems may occur more readily than adaptations in brain regions associated with physical dependence.
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PMID:Biochemical adaptations in the mesolimbic dopamine system in response to heroin self-administration. 886 61

Presents a clinician's viewpoint on the tolerance of and dependence on opiates and opioids in total anesthesia and management of acute (postoperative) and chronic (cancer) pain. Clinical observations are assessed with due consideration for the theoretical (pharmacological) studies. The author analyzes prolonged therapy with different opiates and opioids and the short-term use in massive doses at different stages of surgery. Tolerance to morphine rapidly forms during therapy of chronic pain, and the narcotic doses have to be progressively increased. Tolerance to opioids, such as tramal and buprenorphine, is less expressed. These agents are less hazardous as regards drug dependence, which was proven for tramal by the naloxone test. Clinical manifestations of physical dependence on opiates at different stages of surgical treatment are discussed for the first time. The main last-generation opiates are characterized (tramal, buprenorphine, nalbufin, butorphanol, prosidol) by their capacity to cause physical and mental dependence. The author emphasizes the importance of a proper selection of opiates, opioids, and combinations thereof with the optimal nonopiate components in general anesthesia, postoperative analgesia, and treatment of chronic pain in order to improve the efficacy and narcological safety of analgesia.
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PMID:[The problem of opioid tolerance and dependence during clinical use thereof]. 897 62

This article provides additional direction for nurses in altering the pain management plan for individuals who are currently abusing chemicals. There is a definition of terms (i.e., chemical dependence, addiction, physical dependence, tolerance, and cross tolerance), to provide a foundation for this clinical practice. A review of the literature explains theories that explain what we find occurs clinically: that patients who are chemically dependent require more narcotic to control their postoperative pain.
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PMID:Chemical abuse and pain management. 906 Mar 49

The term drug dependence refers to psychic dependence (addiction), physical dependence, or both, in someone who administers a drug periodically or continuously. Recreational drug abusers are at risk for occlusive and hemorrhagic stroke of diverse cause. Although sometimes over diagnosed, cerebral vasculitis has been historically verified in users of legal and illegal drugs.
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PMID:Vasculitis owing to substance abuse. 936 74

Self-report symptom profiles for nicotine psychic dependence and nicotine physical dependence were examined in data obtained from 363 male and 82 female smokers. The subjects consisted of 363 healthy volunteer and 82 alcoholics. The questionnaire used in this study, consisted of items of the ICD-10 and DSM-IV. The ratio of nicotine dependence diagnosed according to the ICD-10 criteria was lower in alcoholics (22.0%) than in non-alcoholics (54.4%). A total of 19.4% of alcoholics experienced "progressive neglect of alternative pleasures or interest in favour of smoking"; however, only 2.2% of non-alcoholics had the same experience. Although the ratio of nicotine physical dependence diagnosed using the DSM-IV criteria (nicotine withdrawal), was 4.9% in alcoholics, only 0.3 % of non-alcoholics exhibited nicotine physical dependence. These results indicate that the potential for nicotine dependence is not higher than that for other drug dependence and suggested that nicotine physical dependence potential is not much stronger than that reported among social smokers.
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PMID:[Epidemiological studies on tobacco smoking and dependence in Hokkaido prefecture--relation to alcoholism]. 970 1

The present review discusses the potential of nicotine psychic and physical dependence. Since the 1964 Surgeon General's Report on Smoking and Health, much attention has been given to nicotine dependence. Many epidemiological studies indicated that about 50% of smokers could be nicotine dependent; however, few of them had the experience of "progressive neglect of alternative pleasures or interest in favour of smoking." Additionally, some clinical and experimental data indicated that nicotine could not be considered more addictive than cocaine and morphine. As to the physical dependence on nicotine, the nicotine withdrawal syndrome is reported to be observed in about 30% of smokers. However, symptoms of the nicotine withdrawal syndrome are not specific but can appear in smokers put under stress. Several investigators have reported that signs of nicotine withdrawal in experimental animals are weaker than those with opioids, barbiturates and alcohol, and have indicated that it is unclear whether behaviors observed in animal models of nicotine physical dependence are signs of the nicotine withdrawal syndrome. From the current review, it can be considered that the potential for nicotine dependence may not be higher than that for other drug dependence and that nicotine physical dependence potential may be weaker than hitherto believed.
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PMID:[Tobacco dependence]. 984 75

We have established a rat model that reflects the course of development of alcohol and opiate addiction. The present study with d-amphetamine aimed to define general principles in the development of an addiction. Male rats had a continuous free choice between d-amphetamine solutions (100, 200 and 400 mg/l) and water for 47 weeks. An initial intake of high doses of d-amphetamine during the first weeks of drug choice was followed by an individually stable pattern of drug consumption of moderate drug doses. During this period of controlled consumption (from week 10 to week 40), the voluntary intake of d-amphetamine depended on individual factors (dominant rats: 0.37+/-0.02 mg/kg per day, subordinate rats: 0.57+/-0.05 mg/kg per day) and environmental variables (group housing: 0.21+/-0.02 mg/kg per day, single housing: 0.41+/-0.03 mg/kg per day). Beginning with week 41, voluntary d-amphetamine consumption progressively increased (1.9+/-0.2 mg/kg per day in week 47), although the experimental conditions remained unchanged. Drug intake during a retest (free choice as before) after 6 months of drug deprivation revealed that the rats had persistently lost their control over drug intake and were no longer able to adjust drug taking to internal and external conditions. These addicted rats took very high drug doses, even when all d-amphetamine solutions but not water were adulterated with bitter tasting quinine (6.6+/-0.6 mg/kg per day; age-matched controls: 0.37+/-0.04 mg/kg per day). Forced intake of d-amphetamine for 47 weeks (7.1+/-0.3 mg/kg per day) via the drinking fluid caused physical dependence (hyperreactivity during withdrawal) but did not lead to drug addiction (voluntary intake in the retest with adulteration: 0.42+/-0.04 mg/kg per day). Both the temporal development and the prerequisites of psychostimulant addiction were in principle the same as for alcohol and opiates.
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PMID:The development of addiction to d-amphetamine in an animal model: same principles as for alcohol and opiate. 988 28

Long-term administration of morphine for chronic non-malignant pain continues to be controversial, mainly because of the fear of opioid addiction and abuse. It is important to distinguish three phenomena: tolerance of the analgesic and side-effects of the drug, physical dependence (which is a pure pharmacological event) and addiction (defined as a compulsive drug-related behaviour). Animal studies suggest that similar mechanisms underlie tolerance and physical dependence. These may result from an imbalance between anti- and pro-nociceptive mechanisms. By contrast, the occurrence of an addictive behaviour depends on both different endogenous mechanisms and environmental factors. Clinical data suggest that the use of stable doses of morphine (or other opiates) is common in patients suffering from chronic non-malignant pain. However, drug addiction might develop in 'at-risk patients' and therefore the decision to start long-term treatment with an opiate should be undertaken very cautiously, and ongoing assessment of aberrant drug-related behaviours should be undertaken repeatedly.
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PMID:[Tolerance and dependence on opioid analgesics: experimental and clinical aspects]. 1096 10

It has been suggested recently that the endocannabinoid system might be a component of the brain reward circuitry and thus play a role not only in cannabinoid tolerance/dependence, but also in dependence/withdrawal to other drugs of abuse. Here we have examined the changes in endocannabinoid ligands and their receptors in different brain regions, with particular attention to those areas related to reinforcement processes, during dependence on the powerful addictive drug, morphine. Thus, we analysed the brain contents of N-arachidonoylethanolamine (anandamide, AEA), the first discovered endocannabinoid, in rats subjected to daily injections of increasing doses of morphine, according to a schedule designed to render the animals opiate-dependent. Although evidence of physical dependence was assured by the appearance of somatic and neurovegetative responses in these animals after an acute challenge with naloxone, there were no changes in the contents of this endocannabinoid in any of the brain regions analysed. By contrast, we observed a significant decrease in the specific binding for CB(1) receptors in the midbrain and the cerebral cortex of morphine-dependent rats, with no changes in the other regions. The decrease in the cerebral cortex was, however, accompanied by a rise in the activation of signalling mechanisms by CB(1) receptor agonists, as revealed by WIN-55,212-2-stimulated [(35)S]GTPgammaS binding, whereas a reduction in this parameter was measured in the brainstem of morphine-dependent rats. In summary, the present data are indicative of the existence of an alteration of the endocannabinoid transmission during morphine dependence in rats, although the changes observed were region-dependent and affected exclusively CB(1) receptors with no changes in endocannabinoid levels. Because the changes occurred in regions of the midbrain, the cerebral cortex and the brainstem, which have been implicated in drug dependence, our data suggest that pharmacological manipulation of the endocannabinoid system might be a novel tool to reduce morphine addiction.
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PMID:Region-dependent changes in endocannabinoid transmission in the brain of morphine-dependent rats. 1285 Jul 74


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