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)

It is known that the CXBK inbred strain of mouse is deficient in mu1 opioid receptors, whereas the strain has a delta opioid receptor population that is less consistently altered. In the present study, we compared physical dependence on morphine between CXBK and C57BL/6 mice. Both strains of mice were treated with morphine-admixed food for 5 days. During the treatment, the two strains of mice showed no signs of toxicity. There was no significant difference in morphine intake during the treatment between CXBK and C57BL/6 mice. After the treatment, the withdrawal was precipitated by injecting naloxone (0.01-30 mg/kg, s.c.). CXBK mice showed weight loss, diarrhea and ptosis, but not jumping and body shakes after low dose of naloxone. Whereas, C57BL/6 mice showed weight loss, diarrhea, ptosis, body shakes and jumping. These results suggest that naloxone-precipitated weight loss, diarrhea and ptosis may be mediated by mu2 and/or delta opioid receptor, while naloxone-precipitated jumping and body shakes may be mediated by mu1 opioid receptors.
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PMID:The role of mu1 receptor in physical dependence on morphine using the mu receptor deficient CXBK mouse. 131 92

The effect of pretreatment with a delta opioid receptor antagonist, naltrindole (NTI), on the development of physical dependence on morphine was investigated in mice. Several withdrawal signs, an increase in cortical noradrenaline (NA) turnover and a decrease in dopamine (DA) turnover in the limbic forebrain were observed following naloxone challenge in morphine-dependent mice. Pretreatment with NTI (0.3-5 mg/kg, s.c.) during chronic morphine treatment dose-dependently suppressed the behavioral and biochemical changes after withdrawal. The blocking effects of NTI suggest that delta opioid receptors may play a significant role in modulating the development of physical dependence on morphine.
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PMID:Effect of naltrindole on the development of physical dependence on morphine in mice: a behavioral and biochemical study. 756 99

The effect of (+-)-4-((alpha-R*)-alpha-((2S*,5R*)-4-allyl-2,5-dimethyl-1- piperazinyl)-3-hydroxybenzyl)-N,N-diethylbenzamide (BW373U86), the first potent nonpeptidic, highly selective delta opioid receptor agonist, on morphine dependence was studied in rats. Continuous infusion of BW373U86 by a subcutaneously implanted osmotic minipump did not induce any abnormal behavior. After 6 days of BW373U86 infusion, intraperitoneal injection of a high dose of naloxone or naltrindole did not precipitate morphine-like abstinence syndromes. Furthermore, a single injection of BW373U86 did not induce abstinence syndromes or modulate morphine abstinence precipitated by naloxone in chronic morphine-treated rats. However, naloxone-precipitated abstinence syndromes in morphine-dependent rats were partially suppressed by BW373U86 in a dose-dependent manner when the compound was infused subcutaneously before and throughout morphine treatment. Abstinence signs such as wet-dog shake, forelimb tremor and teeth chattering were either suppressed or the intensity was significantly attenuated in these BW373U86-infused rats. This effect was antagonized by naltrindole. These data show that chronic infusion of BW373U86 does not produce physical dependence and that it attenuates some abstinence behaviors in morphine-dependent rats via delta opioid receptors.
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PMID:A nonpeptidic delta opioid receptor agonist, BW373U86, attenuates the development and expression of morphine abstinence precipitated by naloxone in rat. 824 63

Pharmacological data from several laboratories support a modulatory role for the delta opioid receptor in morphine analgesia, tolerance, and physical dependence. We examined the role of the delta opioid receptor in these processes using an in vivo antisense strategy in mice. Intracerebroventricular administration of a 20mer antisense or a mismatch control oligodeoxynucleotide (ODN) targeting the mRNA of the cloned delta opioid receptor (DOR-1) for 3 days did not affect baseline nociceptive thresholds or morphine analgesia compared to untreated or saline-treated mice. However, dose-response studies indicate that the induction of morphine tolerance following 3 days of chronic morphine administration was blocked in antisense but not mismatch ODN or saline-treated mice. Antisense ODN treatment also blocked the development of acute morphine dependence, whereas similar protection was not afforded to mice treated with saline or mismatch ODN. This study demonstrates the relevance of the cloned DOR-1 in morphine tolerance and dependence and provides new evidence for a modulatory role of the delta opioid receptor using this novel approach.
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PMID:An antisense oligodeoxynucleotide to the delta opioid receptor (DOR-1) inhibits morphine tolerance and acute dependence in mice. 886 95

The existence of mu, delta and kappa opioid receptors in the central nervous system is well documented. The present review focuses on the relationships between opioid receptor types and physical and psychic dependences. Mu and delta, but not kappa opioid receptor agonists produce physical dependence. From behavioral, biochemical and molecular biological studies, it is suggested so far that development of physical dependence on morphine results predominantly from an activation of mu 1 and mu 2 opioid receptors which causes functional changes in Gi/o, adenylate cyclase, protein kinases A and C, beta-adrenoceptor and NMDA receptor in the locus coeruleus. Recently, there have been significant advances in studies on psychic dependence. Mu and delta opioid receptor agonists produce psychic dependence, but kappa opioid receptor agonists rather produce an aversive effect. Activation of the mesolimbic dopamine system may lead to psychic dependence on opioids. Mu and delta 1 opioid receptor agonists activate the mesolimbic dopamine system to induce a rewarding effect, whereas the rewarding effect of delta 2 opioid receptor agonists may be produced through a non-dopaminergic system. There are complicated interactions among opioid receptor types. The activation of kappa opioid receptor suppresses physical and psychic dependences on mu and delta opioid receptor agonists, but the activation of delta opioid receptor potentiates the dependence on mu opioid receptor agonists. The clinical use of morphine in patients with cancer pain won't develop dependence probably due to the balance of the opioid system coming from these interactions.
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PMID:[Opioid receptor types and dependence]. 916 Mar 46

The effects of the highly selective delta opioid receptor antagonists naltrindole (NTI) for delta 1 and delta 2 naltriben (NTB) and naltrindole 5'-isothiocyanate (5'-NTII) for delta 2 and 7-benzylidenenaltrexone (BNTX) for delta 1 on the development of physical dependence on morphine were investigated in mice. Neither NTI (3 mg/kg, sc), NTB (0.5 mg/kg, sc), 5'-NTII (0.5 mg/kg, sc) nor BNTX (0.5 mg/kg, sc) suppressed the antinociception induced by morphine (10 mg/kg, sc). Pretreatment with NTI (3 mg/kg, sc), NTB (0.5, 1.0 mg/kg, sc) or 5'-NTII (0.5, 1.0 mg/kg, sc) during chronic treatment with morphine for 5 days significantly suppressed naloxone-induced body-weight loss in morphine-dependent mice. The incidence of jumping and body shakes in morphine-dependent mice that were pretreated with NTI. NTB or 5'-NTII were significantly lower than with morphine alone. Pretreatment with BNTX (0.5, 1.0 mg/kg, sc) during chronic treatment with morphine also significantly suppressed naloxone-induced body-weight loss in morphine-dependent mice, but this suppression was weaker than that by the antagonists. In contrast to mice that had been pretreated with NTI, NTB or 5'-NTII, the incidence of several withdrawal signs, such a jumping and body shakes, was not significantly affected in morphine-dependent mice that were pretreated with BNTX. These findings suggest that both delta 2 and delta 1 opioid receptors may play important roles in modulating the development of physical dependence on morphine.
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PMID:Involvement of delta 1 and delta 2 opioid receptor subtypes in the development of physical dependence on morphine in mice. 916 85

This study investigated the effect of delta opioid receptor blockade by naltrindole on the development of physical dependence and tolerance to the antinociceptive and respiratory depressive effects of morphine in rats. Chronic morphine was delivered either by s.c. injection of increasing amounts of morphine over 5 days or by s.c. implantation of morphine pellets. Animals were cotreated with saline or naltrindole. Antinociception and respiratory depression were assessed after administration of a challenge dose of morphine, and withdrawal signs were determined after naloxone challenge. Naltrindole significantly attenuated the development of antinociceptive tolerance after all three chronic treatment regimens. In addition, rats pretreated with naltrindole displayed significantly fewer withdrawal symptoms and less weight loss after a naloxone challenge. In contrast, naltrindole did not prevent the development of tolerance to morphine-induced respiratory depression. These results imply that tolerance to antinociception and physical dependence involves adaptations at interacting mu and delta receptor populations, whereas tolerance to respiratory depression reflects actions of independent mu and delta receptor populations. These findings suggest that delta antagonists may have potential clinical application for decreasing the rapid development of tolerance to opiate-induced analgesia, while allowing for the development of protective tolerance to respiratory depression.
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PMID:Differential effects of naltrindole on morphine-induced tolerance and physical dependence in rats. 919 Aug 71

The effect of intracerebroventricular (i.c.v.) treatment with antisense oligodeoxynucleotide (A-oligo) to delta opioid receptor mRNA on the morphine-induced place preference and naloxone-precipitated jumping was examined in morphine-dependent mice. Morphine (5 mg/kg, s.c.) produced a significant place preference. I.c.v. pretreatment with A-oligo (0.01-1 microg/mouse) dose-dependently attenuated this morphine (5 mg/kg, s.c.)-induced place preference, while mismatched oligodeoxynucleotide (M-oligo; 1 microg/mouse, i.c.v.) was ineffective. Naloxone (3 mg/kg, s.c.) precipitated jumping in morphine-dependent mice. I.c.v. pretreatment with A-oligo (1 microg/mouse) attenuated this naloxone (3 mg/kg, s.c.)-precipitated jumping in morphine-dependent mice, while M-oligo (1 microg/mouse, i.c.v.) was ineffective. These data demonstrate that the selective reduction in supraspinal delta opioid receptor function caused by pretreatment with A-oligo attenuated the morphine-induced place preference and naloxone-precipitated jumping in morphine-dependent mice, suggesting that the rewarding effect of and physical dependence on morphine may be modulated by central delta opioid receptors.
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PMID:Antisense oligodeoxynucleotide to delta opioid receptors attenuates morphine dependence in mice. 930 58

Previous experiments have shown that mice lacking a functional delta-opioid receptor (DOR-1) gene do not develop analgesic tolerance to morphine. Here we report that mice lacking a functional gene for the endogenous ligand preproenkephalin (ppENK) show a similar tolerance deficit. In addition, we found that the DOR-1 and ppENK knock-outs as well as the NMDA receptor-deficient 129S6 inbred mouse strain, which also lacks tolerance, exhibit antagonist-induced opioid withdrawal. These data demonstrate that although signaling pathways involving ppENK, DOR, and NMDA receptor are necessary for the expression of morphine tolerance, other pathways independent of these factors can mediate physical dependence. Moreover, these studies illustrate that morphine tolerance can be genetically dissociated from physical dependence, and thus provide a genetic framework to assess more precisely the contribution of various cellular and molecular changes that accompany morphine administration to these processes.
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PMID:Genetic dissociation of opiate tolerance and physical dependence in delta-opioid receptor-1 and preproenkephalin knock-out mice. 1248 85

Opioid drugs produce their pharmacological effects by activating inhibitory guanine nucleotide-binding regulatory protein-linked mu, delta, and kappa opioid receptors. One major effector for these receptors is adenylyl cyclase, which is inhibited upon receptor activation. However, little is known about which of the ten known forms of adenylyl cyclase are involved in mediating opioid actions. Here we show that all of the major behavioral effects of morphine, including locomotor activation, analgesia, tolerance, reward, and physical dependence and withdrawal symptoms, are attenuated in mice lacking adenylyl cyclase type 5 (AC5), a form of adenylyl cyclase that is highly enriched in striatum. Furthermore, the behavioral effects of selective mu or delta opioid receptor agonists are lost in AC5-/- mice, whereas the behavioral effects of selective kappa opioid receptor agonists are unaffected. These behavioral data are consistent with the observation that the ability of a mu or delta opioid receptor agonist to suppress adenylyl cyclase activity was absent in striatum of AC5-/- mice. Together, these results establish AC5 as an important component of mu and delta opioid receptor signal transduction mechanisms in vivo and provide further support for the importance of the cAMP pathway as a critical mediator of opioid action.
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PMID:Adenylyl cyclase type 5 (AC5) is an essential mediator of morphine action. 1653 60


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