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)

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.
 ...
PMID:The development of addiction to d-amphetamine in an animal model: same principles as for alcohol and opiate. 988 28

The immunomodulatory effects of dihydroetorphine were systematically investigated in subchronically treated mice. In a dose-dependent fashion, dihydroetorphine (total doses at 444.5, 889 and 1778 microg/kg) lowered the increase of body weight, decreased the weight of the spleen and thymus, weakened the delayed-type hypersensitivity, reduced the generation of antibody-forming cells, inhibited splenic lymphocyte proliferation induced by concanavalin A and lipopolysaccharide, suppressed the production of interleukin-2 in the supernatant of splenocytes induced by concanavalin A, and depleted the ratio of CD4+ and CD8+ subpopulations. Moreover, the physical dependence on dihydroetorphine was also evaluated to confirm that the immunosuppression was concomitant with the addiction to the drug. These results demonstrate that subchronic treatment with dihydroetorphine dose dependently suppresses both humoral and cell-mediated immune function, and that the immunosuppressive effects of dihydroetorphine are much more potent than those of morphine.
 ...
PMID:Immunosuppressive effects of dihydroetorphine, a potent narcotic analgesic, in dihydroetorphine-dependent mice. 1008 8

Prolonged and excessive intake of alcoholic beverages can lead to addiction, increased tolerance and physical dependence as in the case of other drugs. It is the cause of many deaths due to cirrhosis, cancer and accidents. It favours numerous symptoms and disorders that can be reversible on withdrawal of alcohol. Alcohol is not toxic. Taken in regular and moderate fashion (20 to 30 g of alcohol per day), alcoholic beverages play a psychosocial role that gives a certain pleasure. In addition, many concordant epidemiologic studies support the notion that overall morbidity and mortality are significantly less than in those who abstain. The benefit is particularly evident in mortality due to cardiovascular events, but also in senile dementia and osteoporosis. However, there are no data confirming a cause and effect relationship. Despite this potentially favourable role, it cannot be recommended to suggest the use of alcohol to those who abstain, given the possibility that some might subsequently develop alcohol dependence.
 ...
PMID:[Beneficial and deleterious effects of alcoholic beverages]. 1031 84

The objective of this study was to assess the perceptions and reported practices of osteopathic physicians in the diagnosis and treatment of addiction. Copies of survey questions were sent to the 344 members of the West Virginia Osteopathic Society. A total of 176 (51.2%) physicians responded; of these responses, 166 surveys were used for analysis. Respondents included 130 practicing physicians and 36 physicians in internship or residency training programs. Of those responding, 133 were men and 33 were women, and ages ranged from 24 to 81 years with a mean of 41.6 years. Respondents who were graduates of the West Virginia School of Osteopathic Medicine numbered 132 (79.5%), and 99 (59.6%) were in family practice. Characteristics most commonly attributed to addiction were a chronic nature and psychological or physical dependence. More than half of the test subjects did not consider addiction to be a primary disease independent of other factors or psychiatric conditions. Respondents reported a mean addiction prevalence of 20.4%, with the most common substances reported as tobacco, alcohol, and benzodiazapines, respectively. Individual prevalence reports varied from 0% to 95% (SD +/- 20.4%). The most commonly used diagnostic tools were the CAGE (Cut down, Annoyed, Guilty, and Eye-opener) test, DSM III-R (Diagnostic and Statistical Manual of Mental Disorders, 3rd edition, revised) or DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, 4th edition) criteria, and quantity and frequency questions. Medical sequelae such as jaundice or emphysema were the most likely reasons for the respondents to address a substance abuse problem. For referral resources, respondents were most likely to use inpatient or outpatient treatment. A mean success rate of 27.7% was reported by the 133 physicians responding. The wide variance in reported prevalence and the low success rate reported in comparison to that demonstrated in published treatment studies indicate that there is a need for further education of both physicians in training and those presently in practice. Medical sequelae are frequently irreversible signs of late-stage addiction, and physicians should be urged to include such tools as the CAGE test in each regular physical to facilitate earlier intervention.
 ...
PMID:Perceptions and reported practices of osteopathic physicians in diagnosing and treating addiction. 1052 83

Naltrexone, a long-acting, orally effective, opioid antagonist which blocks opioid effects as well as the development of physical dependence, would appear to be a drug ideally suited to addiction treatment. An optimal dosage regimen is critical for the treatment patient compliance in ambulatory opiate detoxification programs. The ideal dosage regimen would be an oral controlled-release system of naltrexone that allowed once-a-day administration providing stable plasma levels. A naltrexone-Eudragit L complex was produced in aqueous medium from naltrexone hydrochloride solution and Eudragit L30D (30% w/v) previously diluted (6% w/v) and partially neutralized. The antagonistic activity of naltrexone-Eudragit L on morphine-induced thermal antinociception, in comparison with conventional naltrexone, was evaluated, using the mouse hot-plate model. Mice were administered 10 mg kg(-1) morphine subcutaneously, 10 min before test, and the antagonist products, either naltrexone-Eudragit L or naltrexone hydrochloride, were administered orally at 0.5, 1, 2, 4, 6, 8, 10, 12, 14 and 16h before the test. The results showed that the antagonism induced by naltrexone-Eudragit L was effective until 12 h after drug administration, while that induced by naltrexone hydrochloride disappeared 10 h after its administration. A 23.47% increase of the area under curve was obtained when naltrexone-Eudragit L was administered, compared with that induced by conventional naltrexone. The time taken to decrease the inhibition of analgesic activity to 50% was delayed by 51.80%. This complexation technique can be considered as a useful tool in the design of oral controlled-release systems capable of inducing a long-lasting effect in-vivo.
 ...
PMID:Preclinical study of an oral controlled release naltrexone complex in mice. 1087 42

Long-term intake of a psychoactive drug alters brain signal transduction, emotional and motivational factors and behavioral parameters. Some effects that outlast long periods of abstinence are due to the long-term presence of the drug in the organism (tolerance, physical dependence). Withdrawal symptoms, as a consequence of physical dependence, can be protracted, i.e. they persist after long periods of drug deprivation (e.g. a desensitization of the production of cAMP). Further persisting effects include experience-based learning. At least three distinct processes can be differentiated: a memory of drug effects (reflected by a sensitization to drug effects etc.), a memory of drug use (reflected by controlled drug consumption), and a memory of addiction (reflected by a persisting loss of control over drug intake and correlating changes in striatal dopaminergic neurotransmission). The latter probably consists of two components: a general memory of loss of control and a specific memory of the addictive drug (general principles for the development of addiction, specific of the urge for the addictive drug).
 ...
PMID:Persisting consequences of drug intake: towards a memory of addiction. 1094 4

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.
 ...
PMID:[Tolerance and dependence on opioid analgesics: experimental and clinical aspects]. 1096 10

Adaptive changes in gene expression are thought to contribute to dependence, addiction and other behavioral responses to chronic ethanol abuse. DNA array studies provide a nonbiased detection of networks of gene expression changes, allowing insight into functional consequences and mechanisms of such molecular responses. We used oligonucleotide arrays to study nearly 6000 genes in human SH-SY5Y neuroblastoma cells exposed to chronic ethanol. A set of 42 genes had consistently increased or decreased mRNA abundance after 3 days of ethanol treatment. Groups of genes related to norepinephrine production, glutathione metabolism, and protection against apoptosis were identified. Genes involved in catecholamine metabolism are of special interest because of the role of this pathway in mediating ethanol withdrawal symptoms (physical dependence). Ethanol treatment elevated dopamine beta-hydroxylase (DBH, EC 1.14.17.1) mRNA and protein levels and increased releasable norepinephrine in SH-SY5Y cultures. Acute ethanol also increased DBH mRNA levels in mouse adrenal gland, suggesting in vivo functional consequences for ethanol regulation of DBH. In SH-SY5Y cells, ethanol also decreased mRNA and secreted protein levels for monocyte chemotactic protein 1, an effect that could contribute to the protective role of moderate ethanol consumption in atherosclerotic vascular disease. Finally, we identified a subset of genes similarly regulated by both ethanol and dibutyryl-cAMP treatment in SH-SY5Y cells. This suggests that ethanol and cAMP signaling share mechanistic features in regulating a subset of ethanol-responsive genes. Our findings offer new insights regarding possible molecular mechanisms underlying behavioral responses or medical consequences of ethanol consumption and alcoholism.
 ...
PMID:Expression profiling of neural cells reveals specific patterns of ethanol-responsive gene expression. 1109

This article presents a perspective on addiction that not only substantiates why group therapy is the treatment of choice for addiction, but also integrates diverse perspectives from 12-step abstinence-based models, self psychology, and attachment theory into a complementary integrative formula. Attachment theory, self psychology, and affect regulation theory characterize addiction as an attachment disorder induced by a person's misguided attempt at self-repair because of deficits in psychic structure. Vulnerability of the self is the consequence of developmental failures and early environmental deprivation leading to ineffective attachment styles. Substance abuse, as a reparative attempt, only exacerbates that condition because of physical dependence and further deterioration of existing physiological and psychological structures. Prolonged stress on existing structures leads to exaggerated difficulty in the regulation of affect, which leads to inadequate modulation of appropriate behavior and self-care and increased character pathology.
 ...
PMID:Addiction as an attachment disorder: implications for group therapy. 1119 96

Opioids are not always available in many developing countries, including those in Latin America. In this study we analyzed the national laws on opioids and other controlled substances from Argentina, Colombia, Costa Rica, Peru, Mexico, and the state of Texas, according to the principles set by the World Health Organization (WHO) and the International Narcotics Control Board (INCB), as well as to the presence of over-regulations regarding their medical and scientific use. The six main principles outlined by WHO and INCB for opioid availability were analyzed by using a total of 17 criteria as shown in Table 3. The result scores ranged from 17/17 (full compliance with all criteria) to 0/17 (non-compliance). Results showed that with the exception of the state of Texas 16/17 (94%), the countries failed to adequately meet the INCB and WHO criteria: Argentina: 7/17 (41%); Colombia: 9 /17 (53%); Costa Rica: 9/17 (53%); Mexico: 4/17 (24%); and Peru: 7/17 (41%). In all 5 Latin American countries, national laws and regulations imposed limits on the number of days allowed for prescription, the potency of the dosage, and the number of doses allowed per day. In all cases, including Texas, there was confusion on the meaning and utilization of the terms physical dependence, psychological dependence, addiction, tolerance and abuse. In total, combining all cases, only 51% of the criteria were met. Additionally, all laws and regulations, especially in Argentina, include over regulations and statements that may further interfere with patient access to opioids. The prescription criteria were fully met by the state of Texas and all five countries. These results indicate that there is need to revise the existing laws and regulations in countries with opioid availability problems, and identify the potential barriers, which may be playing a significant role in the access to adequate treatment. Such review seeks to carefully consider all possible criteria, since partial resolution of legislative articles will not result in increased opioid availability.
 ...
PMID:Legislation analysis according to WHO and INCB criteria on opioid availability: a comparative study of 5 countries and the state of Texas. 1127


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>