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

This chapter examines positive and negative reinforcement mechanisms which play a significant role in alcohol abuse and alcoholism. Consideration is given to the role of euphoria and anxiolytic effects of alcohol as the basis of positive reinforcement, and physical dependence and aversive consequence of drinking as the basis of negative reinforcement. The motivational significance of each of these is discussed with respect to various animal models of addiction and clinical and human research. Brain neurochemistry, neuropharmacology and genetic research data are evaluated from the perspective of reinforcement mechanisms involved with alcohol addiction.
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PMID:Alcohol: mechanisms of addiction and reinforcement. 216 35

According to the hypothesis that the development of physical dependence on and tolerance to opiates depends on the inhibition by opiates of L-asparaginase and L-glutaminase activities in the brain, and the blockade by opiates of the aspartatergic/glutamatergic receptors especially NMDA, four female and fourty-four male heroin addicts were included in a double-blind clinical trial. Four mg chlorpromazine (CPZ) was administered every hour and 10 mg diazepam (DIA) every 6 hours to a group consisting of two female and nineteen male inpatients. The remaining subjects received 15 mg non-opioid antitussive dextromethorphan (DM) instead of CPZ. The withdrawn addicts were controlled twice a day and yawning, lacrimation, rhinorrhoea, perspiration, goose flesh, muscle tremor, dilated pupils, anorexia, joint and muscle aches, restlessness, insomnia, emesis, diarrhea, craving and rejection of smoking as abstinence syndrome signs were observed and rated on a scale of 1, 2 and 3 points according to their intensity. All signs, except perspiration and emesis, were significantly less intense in the group given DM + DIA than CPZ + DIA. The other plus points included the immediate stop of craving and the early onset of smoking in DM + DIA group. The results are considered to be supporting evidence for the hypothesis emphasizing the blockade of NMDA receptors by opiates in opiate addiction. Furthermore, the decrease caused by non-opioid NMDA antagonists in the responsiveness of NMDA receptors appears very promising for the treatment of opiate addicts.
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PMID:The treatment of heroin addicts with dextromethorphan: a double-blind comparison of dextromethorphan with chlorpromazine. 218 2

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

Examination of the attitudes and attributions of cigarette smokers has differentiated smokers who believe their behavior is a "sickness" from those who believe they are "hooked." Among other things, the hooked smoker, more than the sick one, believes they are addicted and their chances of stopping smoking are poor. If there is a causal association between the attribution of addiction and perceived prospects of change, as this suggests, it could mean treatment and preventative programs stressing the addictive nature of cigarettes may be counterproductive. However, the present study, using a survey of 105 male and female smokers from the general population, suggests the attribution of addiction is related to a smoker's estimate of their chances of stopping only through a common association that each of these measures has with actual (not necessarily perceived) physical dependence. Caution is needed in the application of cognitive research when related physical measures have not been included in the research design.
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PMID:Physical dependence and attributions of addiction among cigarette smokers. 231 13

These experiments examined the neurochemical mechanisms involved in the development and expression of place conditioning produced by heroin. Conditioned place preferences (CPP) lasting up to 8 weeks were obtained with doses of 50-1000 micrograms/kg heroin, using a regimen shown not to produce physical dependence. Naloxone pretreatment (50 micrograms/kg) during conditioning prevented the acquisition of heroin-induced CPP, but when given only on the test day, naloxone (50 or 1000 micrograms/kg) did not prevent the expression of heroin CPP. Clonidine disrupted the establishment of heroin CPP at 20 micrograms/kg, but disrupted its expression only at debilitating doses (100 and 200 micrograms/kg). Pimozide attenuated the acquisition (100 micrograms/kg) and expression (250 micrograms/kg) of heroin CPP. Together, these results support a role for opioid and catecholamine systems in the acquisition of heroin reinforcement, but they suggest that once heroin CPP is established, its expression in opiate-free subjects is not opiate receptor mediated and is relatively refractory to pharmacological treatments which disrupt acquisition. The data challenge the notion that the conditioned effects of opiates in drug-free animals are related to the release of endogenous opioids, and they also may help to explain why naloxone and clonidine are ineffective in the treatment of opiate addiction.
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PMID:Differential mechanisms in the acquisition and expression of heroin-induced place preference. 249 60

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

Experimental results and theoretical considerations on the biology of alcoholism are devoted to the following topics: genetically determined differences in metabolic tolerance; participation of the alternative alcohol metabolizing systems in chronic alcohol intake; genetically determined differences in functional tolerance of the CNS to the hypnotic effect of alcohol; cross tolerance between alcohol and centrally active drugs; dissociation of tolerance and cross tolerance from physical dependence; permanent effect of uncontrolled drinking behavior induced by alkaloid metabolites in the CNS; genetically determined alterations in the function of opiate receptors; and genetic predisposition to addiction due to innate endorphin deficiency. For the purpose of introducing the most important research teams and their main work, statements from selected publications of individual groups have been classified as to subject matter and summarized. Although the number for summary-quotations had to be restricted, the criterion for selection was the relevance to the etiology of alcoholism rather than consequences of alcohol drinking.
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PMID:Biochemical basis of alcoholism: statements and hypotheses of present research. 300 23

The technique of chronic schedule-induced drug solution intake was used to determine the possible addiction liability of the short-acting benzodiazepine midazolam. Schedule-induction produces polydipsia over a wide range of fluids as a function of the imposed schedule of food availability. The inducing schedule used presented food pellets automatically once per minute, fixed time (FT) 1-min, for 3 h daily. Two groups of rats, drinking either water or 0.05 mg/ml midazolam solution, were exposed to schedule-induction sessions for approx. 2 months. Then, other FT-values (0, 0.5, 3 and 5 min) were instituted on occasion for single sessions. Each of these 'probe' session determinations was done twice. Although midazolam concentration had been adjusted so that the mean group intakes were equal at FT 1-min, probe values greater than 1 min revealed a greater acceptance of midazolam compared to water. This technique produced session midazolam intakes as great as 25 mg/kg. In the next phase, the entire experiment was repeated except both groups were offered a choice between water and midazolam solution during sessions. Only at FT 0 and FT 5-min was there an indication that midazolam was preferred over water. Two additional groups of animals were exposed to the same schedule-induced polydipsia regimen, drinking water and midazolam solution, respectively. Pre-session administration of doses of Ro 15-1788, CGS 8216 (benzodiazepine antagonists) or midazolam had no effects on either water or midazolam intakes, although the higher dose of midazolam (2 mg/kg, s.c) had a moderately suppressive effect on the non-tolerant water-polydipsic group. All groups were tested on occasion for physical dependence on midazolam with an auditory stimulus as the precipitator and midazolam polydipsic groups were found to have a mild to moderate dependence (clonic seizures, running fits).
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PMID:Midazolam oral self-administration. 316 May 67

Opiates exert numerous effects on all levels of the central nervous system, with tolerance and physical dependence (addiction) being characteristics of this drug class. The capacity of the immune system to participate in processes primarily considered to be central nervous system phenomena has been suggested recently by several studies demonstrating the ability of various immune-modifiers to attenuate opiate withdrawal severity. Therefore, the immunomodulator agent, interferon was investigated to determine the effect upon the opiate withdrawal signs in an animal model. The degree of morphine dependence is measured by quantifying the various behavioral signs associated with naloxone-induced withdrawal. Three different preparations of human alpha interferon (alpha-IFN) were investigated to determine the duration of their attenuating effect upon the naloxone-induced abstinence syndrome in morphine-addicted rats. All three preparations of alpha-IFN reduced the severity of the opiate withdrawal (i.e., addiction) signs for several weeks. There were differences in the potency and the duration of the effects among the three different preparations of alpha-IFN.
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PMID:Single injection of three different preparations of alpha-interferon modifies morphine abstinence signs for a prolonged period. 359 38

Experiments were performed to determine whether physical dependence on opiates (CNS phenomena) can be altered by destruction of the immune system. Irradiation, prior to or after chronic treatment with morphine significantly reduced the opiate-withdrawal syndrome as assessed by naloxone-induced abstinence. This study supports the proposition that addiction to opiates is related, at least in part, to interaction between the central nervous system (CNS) and the immune system.
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PMID:Evidence that opiate addiction is in part an immune response. Destruction of the immune system by irradiation-altered opiate withdrawal. 377 11


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