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)

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

Guinea-pig ileum stored for 30 min in Krebs solution and then mounted in Tyrode solution gave reproducible contracture responses to naloxone after brief exposure to morphine. The preparation lasted for several hours and a variety of pharmacological tests could be made. Clonidine, an alpha 2-adrenoceptor agonist, and nifedipine, a calcium channel antagonist, both known to interfere with tolerance and physical dependence, inhibited naloxone withdrawal contractures in a dose related way. Their action seemed to be receptor-mediated since yohimbine and Bay k 8644, respectively, reversed their inhibitory effect.
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PMID:Reproducible withdrawal contractions of isolated guinea-pig ileum after brief morphine exposure: effects of clonidine and nifedipine. 169 56

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

A 70 year old hypertensive patient who had undergone a gastrectomy experienced withdrawal symptoms 10 h after a second epidural injection of morphine (150 micrograms X kg-1) for postoperative analgesia. A clonidine treatment had been stopped 129 h earlier. These symptoms disappeared shortly after a third epidural injection of morphine. Clonidine was then reintroduced. The later progressive interruption of epidural morphine analgesia did not introduce any further symptoms of withdrawal. Since physical dependence on a drug is related to repeated and prolonged administration of that drug, opiate withdrawal symptoms were highly unlikely after epidural morphine used to relieve immediate postoperative pain. Abrupt discontinuation of a long-term treatment by clonidine may produce a withdrawal syndrome, but clinical and biological signs usually occur earlier than noted in this case. Recent experimental and clinical data has provided support for the existence of a complex presynaptic regulation of noradrenergic transmission in the central nervous system, both alpha 2 and opiate receptors being implicated. The activation of such presynaptic receptors inhibits further transmitter release. Suddenly stopping the chronic administration of alpha 2 or opiate agonists was responsible for a rebound excitation of these noradrenergic neurons, inducing a withdrawal syndrome. The related withdrawal symptoms may have resulted from an interaction between the discontinuation of clonidine and the decrease in morphine activity. Practitioners should be warned of this possible side-effects.
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PMID:[Withdrawal syndrome during epidural administration of morphine after stopping treatment with clonidine]. 609 36

Arterial blood pressure and heart rate were measured in unrestrained rats as an index of the autonomic component of the morphine withdrawal syndrome. Physical dependence was produced by a constant infusion of morphine at increasing doses over 7 days. Signs of physical dependence observed during abrupt withdrawal included classical behavioral symptoms such as withdrawal body shakes (WBS) and increased autonomic responsiveness which was indicated by a sustained increase in mean arterial pressure (MAP) up to 23 mmHg. Injection of naloxone in morphine dependent rats also evoked a dose-related increase in MAP to about 40 mmHg. The antiwithdrawal effects of clonidine were tested in this model by pretreating dependent rats with this agent (6-60 micrograms/kg). Clonidine inhibited the pressor response produced by naloxone by 23-60%. These findings indicate that the increase in MAP during opiate withdrawal provides an objective and quantitative index of the intensity of the narcotic withdrawal syndrome in dependent rats.
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PMID:Cardiovascular changes during morphine withdrawal in the rat: effects of clonidine. 668 28