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)

The intracerebral pattern of diffusion of 3H-morphine was studied autoradiographically following continuous infusion (4, 9, and 18 hr; 1 microliter/hr) into the lateral ventricle during hibernation and euthermia (i.e., not hibernating) in ground squirrels (Citellus lateralis). Morphine diffusion into the parenchyma during both states was extensive, resulting in increased autoradiographic optical density of 34 structures examined. The zone of radiolabeled tissue was primarily ipsilateral, and it expanded with increasing duration of infusion. Diffusion into contralateral regions was more evident in hibernation, although the total area of radiolabeled tissue was not significantly greater than that of euthermic animals. The average optical densities of autoradiographs from hibernating brains were significantly greater than those from euthermic animals, suggesting greater accumulation of labeled material during hibernation. These data suggest that neuroactive compounds released into the ventricular space can achieve widespread distribution within the brain during hibernation (in which all physiological parameters are profoundly depressed) as well as during euthermia. Thus, the apparent lack of development of physical dependence to morphine during hibernation is not due to a restricted distribution of morphine in the hibernating brain.
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PMID:Morphine distribution following infusion into lateral ventricle during hibernation and euthermia. 369 94

Morphine-dependent rats can be trained to discriminate between s.c. injections of saline and 0.1 mg/kg of naltrexone. The discriminative effects of naltrexone, measured by the number of trials completed on the naltrexone-appropriate choice lever in a 20-trial avoidance paradigm, derive from stimuli associated with morphine withdrawal. Opiate and nonopiate drugs were injected s.c. and examined for their ability to block naltrexone-induced discriminative effects and loss of body weight in morphine-dependent rats. Seven opiates blocked dose dependently the discriminative effects of naltrexone and loss of body weight. Potency ranged from fentanyl (330 X morphine) to meperidine (less than 1 X morphine); effects were stereoselective for levorotatory isomers. Loperamide, an opiate that does not readily enter the brain, blocked loss of body weight but not discriminative effects, suggesting that discriminative effects are mediated centrally. Nonopiate behavioral depressants, diazepam, haloperidol and pentobarbital, did not substantially affect either dependent variable, but clonidine (0.01-1.0 mg/kg) blocked discriminative effects of naltrexone partially and weight loss completely. The blockade by morphine (30 mg/kg) of naltrexone-induced discriminative effects and weight loss was surmounted by increasing the dose of naltrexone whereas the blockade by clonidine (0.1 mg/kg) was not. Thus, blockade by opiates of effects of naltrexone appears to be due to a competitive interaction at the mu opioid receptor; clonidine has a different mechanism of action. This discrimination paradigm may afford a specific animal model for studying fundamental processes underlying physical dependence on opiates and for evaluating novel pharmacologic approaches for treating opiate withdrawal in humans.
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PMID:Discriminative stimulus effects of morphine withdrawal in the dependent rat: suppression by opiate and nonopiate drugs. 403 2

Morphine exert numerous effects of all levels of the central nervous system with tolerance, physical dependence and withdrawal being characteristic of this drug class. The degree of dependence is directly correlated to the intensity of withdrawal, success in modifying the withdrawal syndrome may shed light on the dynamic of morphine addiction. The present study demonstrated that alpha-interferon (IFN) significantly modifies the naloxone-induced abstinence syndrome in morphine dependent rats. Single cortical neurons recording and microiontophoretic application of IFN, morphine and naloxone failed to support existing hypothesis that IFN effects are mediated through opiate receptors. Since IFN's are widely present in animals bodies, including the brain, and are locally synthesized. Our observation suggests that IFN's are endocoids which serve to prevent tolerance and dependence to endogenous peptides.
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PMID:Interferon as an endocoids candidate preventing and attenuating opiate addiction. 408 Jul 13

1 Morphine and related synthetic surrogates as well as beta-endorphin and methionine enkephalin caused a contractile response of the longitudinal musculature of the terminal colon of Long Evans rats.2 The muscular contraction caused by the narcotic analgesics exhibited stereospecificity, with levorphanol being about 50 times more potent than dextrorphan and (-)-methadone 4 times more potent than (+)-methadone. In addition, the rank order in potency of a homologous series of N-alkyl substituted norketobemidones demonstrated that the activity of these compounds in eliciting contractile responses corresponded to that for analgesic efficacy in the rat and also correlated to the ability of these derivatives to inhibit the muscular twitch evoked by electrical stimulation of the guinea-pig ileum.3 Naloxone blocked the contractile response of the opiates following competitive kinetics; the naloxone pA(2) values for morphine, etorphine, levorphanol and methadone were very close, in spite of the marked differences in potency of these agents.4 The contractile effect of morphine on the rat colon was abolished by incubation of the tissues with tetrodotoxin 2.0 x 10(-7) M or by decreasing the external Ca(2+) level 100 fold. Increasing the external Ca(2+) concentration caused an apparent non-competitive antagonism of the response to morphine.5 Pretreatment of the tissues with hexamethonium 8.3 x 10(-5) M caused a modest antagonism of the morphine effect while atropine 5.8 x 10(-7) M did not significantly modify the morphine contractile effect. In contrast, methysergide 10(-5) M caused a 10 fold increase in the morphine EC(50).6 Colons from rats rendered tolerant-dependent on morphine were markedly less sensitive to the contractile effects of morphine than those from placebo-treated controls. Tolerance to morphine was also accompanied by an increased sensitivity to the contractile effects of 5-hydroxytryptamine (5-HT).7 A marked increase in the spontaneous muscular activity of segments of the terminal colon of rats chronically treated with morphine was found to occur upon removal of the residual morphine in the tissues by repetitive washings. The spontaneous activity was arrested by applications of morphine, suggesting that physical dependence can be demonstrated in vitro in this particular preparation.8 It is concluded that the opiate-induced contractile response is mediated via stereospecific, naloxone-sensitive, opiate receptors and that the muscular response involves the activation of a 5-HT neurone in the nerve terminals of the colon.
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PMID:Contractile effect of morphine and related opioid alkaloids, beta-endorphin and methionine enkephalin on the isolated colon from Long Evans rats. 617 Mar 77

p-Chlorophenylalanine (p-CPA) reduces brain 5-hydroxytryptamine (5-HT) without altering the dopamine and norepinephrine content. Morphine does not influence the 5-HT level, but partly reverses the depletion of 5-HT by p-CPA. Morphine analgesia and toxicity are not affected by p-CPA treatment. p-CPA also has no effect on acute morphine hypothermia, but after chronic treatment of 5-HT-deficient mice the dose--response curve is no longer parallel, which suggests that another mode of morphine hypothermia occurs. p-CPA diminishes morphine-induced running after acute as well as after chronic morphine administration. p-CPA treatment reduces the sensitivity to the naloxone-precipitated withdrawal reaction, but does not affect the development of physical dependence.
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PMID:The influence of p-chlorophenylalanine on different morphine effects. 644 58

Morphine preference and tendency to relapse to morphine tolerance and dependence were studied in rats which were previously made morphine dependent. Tolerance to, and physical dependence on, morphine were initially produced by administration of increasing concentrations of morphine sulphate in 5% sucrose solution for 3 weeks. A test for drinking preference was performed 4 days after the rats had been successfully detoxified and showed no significant signs of morphine dependence. It was found that, while control animals drank only negligible amounts of morphine solution, previously morphine-dependent rats consumed significantly larger volumes of morphine solution and had recurrence of morphine tolerance and dependence. The present findings show that chronic administration of morphine in drinking fluid produces tolerance and physical dependence as well as addiction in rats; the latter definition is exemplified by these animals having a high tendency to relapse after successful drug withdrawal.
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PMID:Morphine preference in rats previously morphine dependent. 653 22

Physical dependence on morphine-type drugs (morphine, codeine and pethidine) in mice were examined by the drug-admixed food method. Mice were treated with drug-admixed food of increasing concentration (1, 2 and 3 mg/g food) every third day for 9 days. Morphine- and codeine-treated mice showed withdrawal signs when they were given naloxone (5 mg/kg, s.c.), while pethidine-treated mice did not show the withdrawal signs. However, mice treated with pethidine-admixed food (1-6 mg/g food) for 28 days showed naloxone precipitated withdrawal signs. Thus, the data obtained with mice indicate that pethidine produces a weak physical dependence. On the other hand, codeine (40 mg/kg, s.c.) and pethidine (100 mg/kg, s.c.) administration suppressed the abrupt withdrawal signs of morphine-dependent mice that were treated with morphine-admixed food, while the withdrawal signs were completely suppressed in mice administered only 5 mg/kg morphine. These results suggest that the physical dependence liability of morphine type drugs can be predicted by the drug-admixed food method.
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PMID:[Assessment of morphine-type physical dependence liability in mice using the drug-admixed food method]. 654 14

An intravenous infusion method is described for rapidly producing physical dependence in rats. Rats were infused with morphine or meperidine for 24 or 48 h at constant rates and the development of physical dependence was assessed by body weight loss after naloxone challenge. Naloxone challenge induced body losses that were dependent upon magnitude, rate and duration of infusion. The steady-state concentrations of morphine (4 mg/kg/h) in serum and meperidine (6 mg/kg/h) in plasma were 4 and 2.5 microgram/ml, respectively. Morphine concentration in the brain in the steady-state (40 mg/kg/h) was 0.7 micrograms 1 g and in the serum was proportional to the infusion rate. Maximum body weight loss was significantly correlated with total amount of infused morphine, but not with the steady-state concentration of the drug in the serum. These results suggest that total doses of infused morphine, not steady-state concentrations, are critical in producing body weight loss.
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PMID:Acute physical dependence induced by continuous intravenous infusion of morphine or meperidine in the rat. 678 39

Morphine treatment during pregnancy was scheduled with the view to reproduce physical dependence in female rats and to investigate the occurrence of a neonatal withdrawal syndrome (NWS) as well as more prolonged effects of the narcotic in the preweaned pups. Administration started 5 days prior to mating with the daily dose of 20 mg/kg i.p. injections. All along gestation, the dosage was gradually increased up to the final dose of 56 mg/kg/day on the 16th day when the treatment was interrupted. Pregnant dams showed behavioral manifestations of narcotic dependence and drug abstinence. At birth, morphine-exposed neonates exhibited (1) an approximate 28% decrease in respiratory rates (p less than 0.001) during the first day of life and (2) excessive crying (p less than 0.001) accompanied by restlessness. These two last features are related to clinical signs of the NWS identified in babies born to narcotic-addicted women. A significant delay in the time of eye-opening and an earlier sexual maturation in females only were also found in the postnatally developing morphine offsprings. The NWS and some other developmental changes were considered in relation to the used animal model and to possible processes involved in narcotic interferences with postnatal physical growth and neurobehavioral maturation.
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PMID:Morphine treatment during rat pregnancy: neonatal and preweaning consequences. 688 93

1 Dermorphin and Hyp6-dermorphin are the first representatives of a new class of potent opioid peptides occurring in amphibian skin. They present the unique feature of having a D-Ala residue incorporated in the peptide molecule. 2 Dermorphin displayed a potent depressive action on electrically stimulated contractions of the guinea-pig ileum and mouse vas deferens preparations. Dermorphin was respectively 57,294, 18 and 39 times more potent than Met-enkephalin, Leu-enkephalin, beta-endorphin, and morphine on the guinea-pig ileum opiate receptors. On the vas deferens receptors, dermorphin was about as potent as the enkephalins and 40 times more potent than morphine. Naloxone was a powerful antagonist to dermorphin in both preparations. 3 Dermorphin produced potent and long-lasting analgesia in mice by intravenous injection, and in rats by intracerebroventricular injection, the ED50 being here of the order of 13-23 pmol/rat. Morphine was 752 and 2170 times less potent, depending on the analgesia test used. At high intracerebroventricular doses analgesia was accompanied by catalepsy. 4 Intracerebroventricular infusion of dermorphin induced development of tolerance and precipitation of withdrawal symptoms upon administration of naloxone. Both tolerance and physical dependence was consistently less marked with dermorphin than with morphine. 5 The minimum sequence requirement for full dermorphin activity was represented by the N-terminal tetrapeptide. The presence of the D-Ala2-residue was of crucial importance.
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PMID:Pharmacological data on dermorphins, a new class of potent opioid peptides from amphibian skin. 719 58


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