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)

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

The endogenous opioid system is often assumed to play a role in vulnerability to drug abuse. However, controversial results have been reported regarding the levels of enkephalins or preproenkephalin in neurons of rodent brains after opiate administration. The present study was performed to determine the extracellular levels of enkephalins and its physiological antagonist cholecystokinin (CCK), using in vivo microdialysis in freely moving rats after morphine-induced physical dependence or positive place conditioning. A large increase (340%) of Met-enkephalin was observed in the periaqueductal gray matter, a structure involved in morphine withdrawal syndrome, in morphine-dependent rats. No change in CCK immunoreactivity occurred in these conditions. Moreover, using the conditioning place preference paradigm, we observed for the first time opposite changes of enkephalin outflow in the nucleus accumbens (NAc). Thus, an increase in enkephalin levels was observed in rats placed in the drug-associated compartment and a decrease in the saline-paired side. These changes in opioid peptides in the NAc may reflect an "emotional state" of the animals in relation to the expectation of drug reward (reinforcing effects of morphine). Moreover, the lack of regulation in CCK outflow suggests that CCK-opioid interactions in morphine dependence involve probably post-receptor events.
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PMID:Chronic morphine treatment modulates the extracellular levels of endogenous enkephalins in rat brain structures involved in opiate dependence: a microdialysis study. 1182 32

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