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)

Chronic ethanol treatment of mice has been shown to result in increased binding of dizocilpine and glutamate to hippocampal NMDA receptors. These changes were suggested to reflect an increase in NMDA receptor number that may underlie certain signs of the ethanol withdrawal syndrome. However, there was no change in binding of a competitive NMDA receptor antagonist, or of ligand binding to the glycine co-agonist site on the receptor after chronic ethanol treatment. Differential changes in the binding of particular ligands at the NMDA receptor suggested the possibility that chronic ethanol ingestion might selectively affect the expression of particular NMDA receptor subunits. Our current work demonstrates that chronic ethanol ingestion by mice, which results in the generation of physical dependence, also produces increases in the NMDA receptor NR1 subunit protein in the hippocampus and cerebellum (approximately 50% and 95%, respectively), and produces increases in the NR2A subunit protein in the hippocampus and cortex (approximately 25% and 40%, respectively). However, the mRNA levels for these subunits were not increased in the respective brain areas by the same ethanol treatment. The changes in NMDA receptor subunit expression in discrete areas of the brain may contribute to the previously observed changes in ligand binding and, possibly, signs of ethanol withdrawal.
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PMID:Regional and subunit specific changes in NMDA receptor mRNA and immunoreactivity in mouse brain following chronic ethanol ingestion. 884 15

Cellular and molecular mechanisms underlying opioid tolerance and dependence remain elusive. We investigated roles of EphB receptor tyrosine kinases--which play important roles in synaptic connection and plasticity during development and in the matured nervous system--in development and maintenance of physical dependence on morphine in the mouse spinal cord (SC). Spinal administration of an EphB receptor blocking reagent EphB2-Fc prevents and/or suppresses behavioral responses to morphine withdrawal and associated induction of c-Fos and depletion of calcitonin gene-related peptide. Western blotting and immunohistochemical fluorescence staining demonstrates that EphB1 receptor protein is significantly up-regulated in the spinal dorsal horn following escalating morphine treatment. Chronic morphine exposure and withdrawal significantly increased phosphorylation of N-methyl-D-aspartate receptor subunit NR2B as well as the activated forms of extracellular signal-regulated kinase and the cAMP response element binding protein in SC. The increased levels of phosphorylation of these molecules, however, are significantly inhibited by the EphB receptor blocker. These findings indicate that EphB receptor signaling, probably by interacting with NR2B in SC, contributes to the development of opioid physical dependence and withdrawal effects. This novel role for EphB receptor signaling suggests that these molecules may be useful therapeutic targets for preventing, minimizing, or reversing the development of opiate dependence.
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PMID:EphB receptor signaling in mouse spinal cord contributes to physical dependence on morphine. 1877 47