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

The investigation examined whether or not physical dependence or other abnormalities were detectable 1--3 months after withdrawal in dependent rats that had been treated with the morphine (amintenance dose of 100 X 2 mg/kg/day, s.c.) for 7 weeks. When narcotic antagonists were administered on the 32nd day after withdrawal, nalorphine caused a dose-dependent increase in spontaneous locomotor activity and a complete inhibition of wet-dog shakes and the writhing syndrome. Naloxone was ineffective. A remarkable increase in spontaneous locomotor activity on the 67th day and a significant increase in body weight on the 69th and 92nd day after withdrawal occurred after an acute injection of morphine (10 mg/kg, s.c.). When morphine (10 mg/kg) was administered for 3 days from the 92nd day after withdrawal, withdrawal from morphine produced a significant decrease in body weight. When morphine (10 mg/kg) was administered for 3 days from the 102nd day after withdrawal, a levallorphan injection caused a significant decrease in spontaneous locomotor activity and an increase in the frequency of the diarrheal syndrome. These abnormal responses, not observed in the naive rats, suggest the remains of some behavioral and biochemical abnormalities 3 months after morphine withdrawal.
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PMID:Some altered responses in rats formerly dependent on morphine. 2 98

Narcotic analgesics and related drugs act as agonists on several receptors that are responsible for their effects on pain perception, mood and feeling state, and respiration, as well as other pharmacologic actions. Naloxone is the first discovered antagonist that is devoid of agonistic activity and appears to be a competitive antagonist at several receptors. The ability of naloxone to displace or prevent the binding of agonistic narcotics is partly responsible for its antagonistic effects. The ability of naloxone to rectify narcotic-depressed homeostats and precipitate abstinence is also related to its antagonistic activity. Certain cautions and principles apply in the use of naloxone in treating narcotic overdose, reversing surgical analgesia, and the treatment of neonates and children. Unapproved uses of naloxine include reversing the psychotomimetic effects of certain agonists-antagonists, terminating narcotic-induced convulsions and coma, reversing non-narcotic depression, diagnosing physical dependence, and treating narcotic addicts.
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PMID:Naloxone. 18 95

Both naloxone and naltrexone are effective narcotic antagonists with minimal agonistic effects and a wide margin of safety. Naloxone is useful in the treatment of narcotic overdose and it is helpful in the quantification of physical dependence. Naltrexone is pharmacologically successful as an orally effective, long-acting antagonist but its clinical usefulness in the prevention of relapse is still being determined.
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PMID:Clinical pharmacology of narcotic antagonists. 36 32

1. A slow release emulsion of naloxone (naloxone SR) was administered subcutaneously to rats in an attempt to induce physical dependence of the morphine type. 2. Naltrexone (2.5 mg/kg), injected i.p., failed to elicit an abstinence syndrome in rats treated with 75, 100 or 150 mg/kg naloxone SR for 24, 48, or 72 h. 3. Naloxone SR had no effect on the whole brain levels of noradrenaline, dopamine, homovanillic acid or serotonin. 4. Naloxone SR caused an apparent dose-related increase in the brain levels of 5-hydroxyindoleacetic acid. 5. These results show that while naloxone does not induce physical dependence of the morphine type, it may, like morphine, increase the brain serotonin turnover rate. 6. It is proposed that the increase in brain serotonin turnover rate may not be causally related to physical dependence on morphine-like drugs but may be a property of drugs containing the basic opiate molecular structure.
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PMID:Dissociation of increased 5-hydroxyindoleacetic acid levels and physical dependence: the effects of naloxone. 56 13

Naloxone-precipitated withdrawal and oral self-administration of morphine were compared in norphine-dependent caudate-lesioned and sham animals. The lesion failed to suppress any signs of withdrawal in the dependent-lesioned animals as compared with the shams. However, the dependent-lesioned animals self-administered less morphine that their sham controls. The withdrawal results differed from others previously reported and it was hypothesized that the possibility of development of processes compensatory to the lesion among animals of this experiment, might account for the difference. The results were also discussed in relation to possible dissociation of mechanisms governing physical dependence and self-administration.
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PMID:Effects of lesions of the caudate nucleus on morphine dependence in the rat. 103 5

mu-Opioid receptors mediate inhibition of the N-type calcium channel current in the human neuroblastoma cell line SH-SY5Y. We have previously shown that chronic exposure to morphine induces homologous tolerance to this effect. Here we show that chronic incubation with morphine (1 microM for three to seven days) does not, however, induce physical dependence at the level of the calcium channel current. Initial experiments were performed using the whole cell voltage-clamp technique. Chronically treated cells were bathed in superfusate which also contained morphine (1 microM). On washout of morphine the current amplitude increased by 12% and this was reversed by re-addition of morphine. Naloxone (1 microM) elicited a similar increase. However, this increase is most likely due to a reversal of the residual inhibitory effect of morphine on the calcium channel current rather than being a novel withdrawal response. Chronic exposure to morphine did not change the voltage-sensitivity of the calcium channel current or induce the appearance of a current sensitive to the L-type calcium channel agonists Bay K 8644 (3 microM) and S(+)-PN 202-791 (1 microM). In a further series of experiments the nystatin-perforated patch technique was employed in order to prevent washout of any L-type current in these cells. Under these conditions a Bay K 8644-sensitive, L-type current was unmasked following treatment with omega Conus Toxin GVIA. The peak current was depressed by omega Conus Toxin GVIA (1 microM) by approximately 90% both in control cells and cells chronically exposed to morphine. Now Bay K 8644 (3 microM) almost doubled the remaining current but the effect was equal in both groups of cells. It is concluded that chronic exposure to morphine does not induce physical dependence and a withdrawal syndrome in the human SH-SY5Y neuroblastoma cell line by changing either N-type or L-type calcium channel activity.
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PMID:Chronic exposure to morphine does not induce dependence at the level of the calcium channel current in human SH-SY5Y cells. 127 57

Two doses of methadone were administered by osmotic minipump from day 8 of gestation through parturition. A pair-fed control group received saline via minipump and was allowed to eat and drink only the amount consumed by the high dose group on the same gestation days. A nontreated control group was left undisturbed during pregnancy. All treated and control litters were fostered at birth to untreated dams. Naloxone challenge of the dams after parturition showed that drug treatment produced physical dependence. Methadone treatment reduced maternal weight gain but had no effect on either the frequency of resorptions or birthweight. Both doses of methadone increased perinatal mortality but only the high dose produced a decrement in postnatal growth. To examine the effects of methadone on the rest-activity cycle of the offspring, groups of three littermates from each of the treated and control groups were tested for an 8 h observation period on electronic activity monitors at 22 days of age. No behavioral effects were observed for either control group or the low dose methadone group. The high dose methadone offspring, however, spent less time resting, showed disrupted rhythmicity, and poor state regulation. These findings are discussed in relation to earlier studies using once per day methadone administration as well as clinical descriptions of infants undergoing opiate abstinence.
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PMID:Prenatal administration of methadone using the osmotic minipump: effects on maternal and offspring toxicity, growth, and behavior in the rat. 159 81

Naloxone, added after contractions induced by CCK-8 on the guinea pig ileum preparation, elicited a contraction attributed to the release of endogenous opioid which could inhibit the excitatory action of the peptide. With large concentrations of CCK-8, the preparation gave reproducible responses with time. Naloxone, added before the peptide, protracted the excitatory response to CCK-8, but not its height. Morphine decreased the response to CCK-8 but simultaneously raised the response to naloxone. The latter effect appeared very similar to the withdrawal contraction observed after brief exposure of the opioid in the guinea pig ileum to opioids. Clonidine, and alpha-2 adrenoceptor agonist, and nifedipine, a calcium channel antagonist, both known to interfere with tolerance and physical dependence, affected the excitatory response to CCK-8 and the subsequent response to naloxone in a different way.
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PMID:Some pharmacological characteristics of the guinea pig ileum opioid system activated by cholecystokinin. 169 57

The effects of constituents of an antitussive and expectorant preparation on physical dependence potential and antitussive activity of dihydrocodeine (DC) were studied. Rats were treated with DC, methylephedrine (ME), chlorpheniramine (CP), and caffeine (CA) singly or simultaneously admixed with food (DC 0.125, ME: 0.25, CP: 0.05, CA: 0.25 mg /g of food) for 7 days. Subsequently, rats were treated with naloxone (0.5 mg/kg, sc) and withdrawal signs produced were observed. Naloxone-precipitated body weight loss in DC-treated rats was suppressed by simultaneous administration of the three drugs (ME, CP and CA) or CP, which is a H1-receptor antagonist. In abrupt withdrawal, the withdrawal signs were also suppressed by CP. Moreover, tripelennamine, the same kind of H1-receptor antagonist, suppressed naloxone-precipitated withdrawal signs, but cimetidine H2-receptor antagonist, did not suppress them. These results may suggest that H1-receptor antagonists suppress the development of physical dependence on DC, and that H1-receptors play an important role in the physical dependence. On the other hand, the cough reflex was induced by electric stimulation in order to evaluate the influence of ME, CP, and CA on antitussive effect of DC in guinea pigs. ME enhanced the effect of DC. These experimental findings suggest that the constituents of the antitussive and expectorant preparation suppress the development of physical dependence on DC, though they increase the antitussive effect of DC.
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PMID:[The effects of constituents of an antitussive and expectorant preparation on physical dependence on and antitussive activity of dihydrocodeine]. 198 Apr 11

Previous studies have demonstrated antagonist-precipitated withdrawal from 45 min to 24 hr after acute opioid administration in nondependent human subjects. The purpose of this study was to examine longer postagonist intervals and to determine the maximum interval between agonist administration and antagonist challenge at which precipitated withdrawal can be observed. During this study 6 nondependent male volunteers who reported using opiates an average of 4 times per week received naloxone challenges (10 mg/70 kg i.m.) at 6, 12, 24, 36, 48, 60, or 72 hr after single i.m. injections of morphine (18 mg/70 kg or 30 mg/70 kg). Each interval was tested independently in random order. Naloxone reliably precipitated withdrawal signs and symptoms at 6 and 12 hr postmorphine. Withdrawal symptoms were greatly diminished in intensity at 24-hr postmorphine and were not elicited at postmorphine intervals longer than 24 hr. Withdrawal precipitation persisted somewhat longer than pupillary constriction because pupils had returned to predrug diameters by 24 hr postmorphine but, generally, there appeared to be correspondence between offset of agonist effects and dissipation of precipitated withdrawal. This study extends observations about the time course of acute physical dependence effects which begin within minutes after acute morphine exposure, dissipate within 36 hr, are associated with the onset and offset of agonist effects and do not require chronic opioid administration.
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PMID:Acute opioid physical dependence in humans: effect of varying the morphine-naloxone interval II. 224 50


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