Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0278080 (physical dependence)
 1,658 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

When given a two-bottle choice between gradually increasing morphine concentrations (in 0.2% saccharin) and plain tap water, C57BL/6J mice consumed almost 90% of their daily fluid intake from the morphine-saccharin bottle, while the DBA/2J strain, in contrast, consumed 13% or less from the morphine-saccharin solution. The C57BL/6J strain consistently consumed mean daily doses of morphine sulfate in excess of 200 mg/kg, which was sufficient to induce an easily discernable withdrawal syndrome upon removal of the morphine solution, either with or without naloxone challenge. Hypothermia, tremor, wet dog shakes, jumping, and diarrhea were prominent withdrawal signs. In separate experiments, the saccharin was removed from the morphine-containing bottle, yet the C57BL/6J mice continued to prefer the morphine solution over tap water. In complete contrast to the above, mice of the DBA/2J strain rejected the morphine-saccharin solution at the lowest concentration employed, and at no time did their mean daily morphine dose exceed 20 mg/kg. Thus, morphine-saccharin preference is strongly genetically determined, and a high degree of physical dependence can result in the morphine-preferring strain. Palatability differences appear not to be the predominant explanation for these differences in morphine-saccharin consumption.
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PMID:Physical dependence induced by the voluntary consumption of morphine in inbred mice. 232 Jun 38

Investigations were performed to determine whether the pharmacodynamic effect of barbital, the development of tolerance to or the physical dependence on the hypnotic are responsible for drug-taking behavior. Three groups of male rats, untreated, tolerant to and physically-dependent on barbital, were given free choice between 0.5% barbital solution and tap water. Drug-taking behavior was estimated according to specified criteria. Initially naive rats rejected an unsweetened barbital solution. Tolerant rats also refused the hypnotic, even after they had experienced abstinence symptoms only once. However, tolerant rats that repeatedly underwent withdrawal after an intake of more than 400 mg/kg/day of barbital did show drug taking behavior. Therefore, several experiences with pronounced abstinence symptoms seem to be necessary for initiating and sustaining barbital drug taking behavior in rats.
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PMID:Repeated withdrawal from barbital as a drive for 'drug taking behavior' in rats. 653 66

Using mice, preference for barbital or ethanol solution was examined in choice test between drug solution and tap water after pretreatment with the drugs for 6, 15 or 30 days under different conditions, a) forcedly given the drug solution as drinking liquid. b) ip injected the drug twice daily, c) combined treatment, forced drinking plus ip injection. Pretreatment with barbital induced aversion to the drug solution regardless the conditions of pretreatments mainly because the unpalatability of the drug solution and also the unpleasant effect of injected drug. In ethanol pretreated animals, pre-exposure to ethanol solution decreased the preference ratio for the drug solution n choice test but accustomed to the taste in parallel with the duration of the pretreatment. After treatment with injection, on the other hand, animals acquired preference for ethanol solution indicating the reinforcing effect of the injected drug. Six days pretreatment with the drugs developed tolerance to their suppressive effect and in barbital treated animals physical dependence was also developed. However, the degree of preference or drug solution was not parallel to the intensity of tolerance or physical dependence. Characteristics of the test drugs as reinforcer of drinking behavior was easily determined by this method and its validity for the screening of the drugs of psychic dependence liability was suggested.
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PMID:[Determination of the development of psychotic dependence to drugs in small animals. 4. Selective drinking of barbital and ethanol solutions by mice]. 689 51

Oral administration of levorphanol solution induces physical dependence in rats within a few days, as demonstrated by abstinence symptoms such as loss of body weight, sensitivity to touch and inversion of locomotor activity after withdrawal from the drug. In order to examine whether the physically dependent rats show an active drug-seeking behaviour they were given successively free choice between sweetened levorphanol solution (LSa) and two alternative drinking liquids -- sweetened tap water (WSa) and unadulterated water (W). In the case of LSa and W the rats chose LSa, but they preferred WSa to LSa. Another group of rats made dependent on unsweetened levorphanol solution (L) had the choice between L and W. They rejected L immediately.
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PMID:Development of dependence on levorphanol in rats by oral intake of the drug -- the influence of taste on drinking behaviour in rats physically dependent on levorphanol. 719 61

The genomic map locations of specific genes controlling behaviors can be identified by studying a panel of recombinant inbred (RI) mouse strains. The progenitor C57BL/6J (B6) and DBA/2J (D2) strains, and 19 of the BXD RI strains derived from an F2 cross of these progenitors, were tested for 3% and 10% ethanol (EtOH) intake. The test sequence began with two-bottle free choice between tap water and unsweetened ethanol, and ended with free choice between water and saccharin-sweetened ethanol. Saccharin preference was also measured. Correlational analyses indicated that 59% of the genetic variance in 10% ethanol and sweetened 10% ethanol consumption was held in common, 24% of the genetic variance in saccharin and sweetened 10% ethanol consumption was held in common, and only 7% of the genetic variance in saccharin and unsweetened 10% ethanol consumption was held in common. These percentages for 3% ethanol solutions were 21%, 36%, and 14%. In addition, the severity of handling-induced convulsions during ethanol withdrawal was found to be significantly associated with the amount of ethanol consumed from the sweetened ethanol drinking tubes, suggesting that genetic differences in avidity for ethanol could lead to the development of physical dependence. Quantitative trait loci (QTL) analyses revealed that several genetic markers were associated with ethanol consumption levels, including markers for the D2 dopamine receptor. QTL analyses of saccharin and sweetened ethanol consumption identified the sac locus, thought to determine the ability to detect saccharin. In general, our results suggest that saccharin and ethanol consumption are determined by the actions of multiple genes (QTL), some in common, and suggest specific map locations of several such QTL on the mouse genome.
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PMID:Localization of genes affecting alcohol drinking in mice. 797 6

A variety of in vitro immune measures were examined in groups of Lewis rats that chronically consumed either tap water or a 0.2, 0.4, or 0.6 mg/ml morphine drinking solution. Rats received a subcutaneous injection of either saline or 15 mg/kg morphine sulfate 1 h before sacrifice. In the drinking groups, the acute morphine injection significantly suppressed splenic natural killer (NK) cell activity, mitogen-stimulated splenic T- and B-cell proliferation and gamma-interferon (gamma-IFN) production. A single, acute injection of morphine did not suppress NK cell activity in rats that drank the two highest concentrations of morphine, whereas it did suppress the mitogen-stimulated splenic T- and B-cell proliferation and gamma-IFN production. These results suggest that rats that drank morphine for 20 days developed tolerance to morphine's suppressive effect on NK cell activity but not to other measures of immune status. Morphine drinking rats also developed tolerance to morphine's antinociceptive effects and revealed signs of physical dependence when the morphine solution was withdrawn or when naltrexone was administered.
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PMID:Tolerance development to morphine-induced alterations of immune status. 925 Apr 73

Two common assessment tools for nicotine dependence are the Fagerstrom Test for Nicotine Dependence (FTND) and the Nicotine Dependence section of the Diagnostic Interview Schedule [(DIS)-III-R or -IV based on the Diagnostic and Statistical Manual (DSM)-III-R and -IV, respectively]. The FTND emphasizes morning smoking and overall "heaviness" of smoking. The DSM emphasizes adverse consequences, desire to cut down, and mood changes during withdrawal. We tested (1) how the DSM-III-R diagnosis of Nicotine Dependence is related to FTND score; and (2) how the (a) DSM-III-R or (b) elevated FTND score is related to longer smoking histories, greater psychiatric symptomatology, and tobacco liking scores. Retrospective chart reviews were conducted on 370 smokers, the majority (55.9%) of whom had a current DSM-III-R diagnosis of Substance Dependence other than nicotine. All subjects had completed the FTND, the DIS-III-R, the Symptom Checklist-90-Revised (SCL-90-R), and a survey on drug liking. Agreement statistics were calculated between the DSM-II-R diagnosis of Nicotine Dependence and various cutoff scores values that were assigned as thresholds for nicotine dependence on the FTND. At no cutoff score did the two instruments reliably agree; the highest kappa (at a cutoff of FTND > or = 7) was 0.205. At cutoffs above 5, the FTND diagnosed fewer cases than the DSM-III-R. Multiple regression analysis showed that DSM diagnosis was associated with greater psychiatric symptomatology on the SCL-90-R, while FTND scores were associated with greater tobacco liking. The FTND and the DSM-III-R appear to measure different aspects of the tobacco dependence process. Specifically, the FTND may provide a stronger measure of physical dependence, while the DSM may tap other domains such as awareness of dependence, behaviors resulting from that awareness, and psychiatric symptomatology. Disagreements between the FTND and the DSM are likely to become greater with the changes in the DSM-IV.
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PMID:The Fagerstrom Test for Nicotine Dependence and the Diagnostic Interview Schedule: do they diagnose the same smokers? 1180 Feb 17

Due to the claim that chronic administration of lithium or L-N(G)-nitroarginine methyl ester (L-NAME), a nitric oxide synthase (NOS) inhibitor reduces morphine withdrawal syndrome, the effects of chronic administration of lithium, L-NAME, or L-arginine (L-Arg), a precursor of NO, alone or co-administration of lithium with L-Arg or L-NAME, on naloxone-precipitated withdrawal syndrome and physical dependence development to morphine in mice chronically treated with morphine, were evaluated. Morphine dependency was induced by the intraperitoneal injection (i.p.) of morphine (10 mg/kg), once daily for 7 days. Physical dependence to morphine was observed by precipitating an abstinence syndrome with naloxone (2 mg/kg, i.p.). Chronic administration of L-NAME (10 mg/kg, i.p., once daily, for 7 days after 10 days of receiving only tap water and food prior to naloxone), decreased all withdrawal signs significantly, while L-Arg (200 mg/kg, as above) increased only some withdrawal signs significantly in morphine-dependent mice. Chronic administration of lithium (600 mg/kg, in drinking water) alone or co-administration of lithium (as above) with L-NAME (10 mg/kg) or L-Arg (200 mg/kg, i.p., once daily) for 7 days after 10 days of receiving only lithium (as above) and food, decreased all withdrawal signs and physical dependence significantly in morphine-dependent mice. The results obtained indicate that co-administration of L-NAME with lithium increases the effect of lithium or L-NAME alone, on withdrawal signs, but this increase is not significantly different as compared to chronic lithium or L-NAME administration alone; while co-administration of L-Arg with lithium decreases the effects of lithium on withdrawal signs and this decrease is not significant as compared to chronic lithium administration alone. These findings indicate that nitric oxide may be involved in modulation of naloxone-induced withdrawal syndrome, and treatment with lithium could have some effect on this system. Copyright 2000 John Wiley & Sons, Ltd.
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PMID:Comparison of simultaneous administration of lithium with L-NAME or L-arginine on morphine withdrawal syndrome in mice. 1240 37