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

The effects of chronic ethanol intake by mice and rats have been determined on brain ribosomes. Under conditions of ethanol administration, when physical dependence on ethanol either does or does not develop in rats, significant inhibition of polypeptide synthesis was observed in comparison with animals not receiving ethanol. In both rats and mice drinking a 10% ethanol solution, in vitro protein synthesis was found to be diminished more in the free than membrane-bound polyribosomes (polysomes) when compared to similar fractions obtained from control animals. Addition of exogenous amino acids stimulated protein synthesis of free polysomes to a greater extent than that of bound polysomes obtained from both groups of micemin vivo incorporation of [5-3H]-orotic acid into RNA was more inhibited in polysomes than ribosomes of ethanol-drinking mice, suggesting that ethanol affects messenger RNA. In addition, chronic ethanol ingestion produced a decreased in vivo incorporation in ribosomal RNA of a mixed population of ribosomes and polysomes. Chronic ethanol ingestion by mice led also to a differential effect on the polysomal population of the brain. It decreased the amount and the incorporation of precursor label into RNA of free polysomes while exerting an opposite effect on bound polysomes. The significance of these findings relative to brain metabolism is discussed.
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PMID:Ethanol and brain ribosomes. 109 40

Administration of ethanol and nutrients to rats thrice daily by gavage for 3 days produced a linear increase in physical dependence during the first 3 days and a 2% increase in body weight. Rates of protein synthesis on free and membrane-bound polysomes in whole brain and in 7 brain regions, comprising the entire brain, were measured in vivo under pool expansion conditions with [3H]leucine at intervals during the development and decay of ethanol dependence. During dependence development there was a progressive decrease in the rate of protein synthesis on free polysomes, but this change was not significant (P less than 0.05) until the third day, and a decrease in the rate on membrane-bound polysomes after 3 days. The inhibition of protein synthesis is attributable to a decreased rate of polypeptide elongation. There was no change in brain weight, DNA content, ribosome content, ribosome distribution of mRNA pool size. There was, however, a decrease in leucine uptake after 3 days. In an attempt to distinguish between the acute effects of ethanol on regional rates of protein synthesis and those changes associated with dependence development, rates were measured 1.5 h after administering a 5 g/kg dose of ethanol to both control and dependent rats. Rates on free polysomes in the hippocampus-amygdala and thalamus-hypothalamus and on membrane-bound polysomes in the cerebellum and hippocampus-amygdala of dependent rats were reduced; however, there was a general reduction in the rates in control rats that may have obscured reductions in other regions from dependent rats. During early withdrawal, 12 h after the last dose of ethanol, there was an increase in the rate of free polysomes in the pons-medulla and striatum-septum and on membrane-bound polysomes in the hippocampus-amygdala, and a decrease in the rate on free polysomes in the cortex and thalamus-hypothalamus and on membrane-bound polysomes in the cortex. After 24 h, there was an increase in the rate on free polysomes in all regions (cerebellum, cortex, mesencephalon, striatum-septum and thalamus-hypothalamus) except the hippocampus-amygdala and pons-medulla and an increase in the rate on membrane-bound polysomes in all regions (cortex, hippocampus-amygdala, mesencephalon, pons-medulla and striatum-septum) except the cerebellum and thalamus-hypothalamus. The possible relationship of these changes to the homeostat hypothesis of ethanol dependence is discussed.
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PMID:Changes in in vivo rates of protein synthesis on free and membrane-bound polysomes in rat brain during the development of physical dependence on ethanol and after the withdrawal of ethanol. 719 28

Administration of ethanol thrice daily to rats in amounts sufficient to induce a high degree of physical dependence resulted in a 20% decrease in the rate of protein synthesis on liver membrane-bound polysomes in vivo after 3 days of treatment without affecting the rate on free polysomes. The inhibition was attributable to a decrease in the rate of polypeptide elongation as evidence by comparable decreases in nascent chain synthesis and completed protein release without any change in leucine uptake by liver. Chronic ethanol treatment did not affect the quantity or distribution of free and membrane-bound polysomes, the DNA concentration, or the weight of liver. The inhibition of protein synthesis on membrane-bound polysomes cannot, therefore, be readily ascribed to ethanol-induced nutritional deficiencies or to some nonspecific toxic effect of ethanol.
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PMID:Differential effect of chronic ethanol administration on rates of protein synthesis on free and membrane-bound polysomes in vivo in rat liver during dependence development. 720 61

The molecular mechanisms associated with ethanol-induced tolerance and physical dependence have yet to be elucidated. In previous studies we have demonstrated that chronic ethanol administration produced a decrease in the GABAA receptor mRNA level of alpha 1, alpha 2, alpha 5 subunits, and a decrease in the polypeptide (alpha 1, alpha 2, and alpha 3) expression in the rat cerebral cortex. In this study we examined the effect of chronic ethanol treatment on the mRNA levels and the expressions of the beta-subunits of the GABAA receptors in rat cerebral cortex. The results indicate that chronic ethanol administration produced an upregulation of the beta 1 subunit mRNA (12 kb) by 29 +/- 10%, beta 2 mRNA (8 kb) by 55 +/- 6% and the beta 3-subunit (6 kb) mRNA by 72 +/- 9% in cerebral cortex. The levels of the beta 2 and beta 3 subunit mRNAs remains elevated at 24 hr withdrawal. We also investigated the effect of chronic ethanol administration on the beta-subunit polypeptide expression using monoclonal antibody BD17, which recognizes the beta 2 (P56) and beta 3 (P58) polypeptides. Chronic ethanol treatment increased the levels of both of these polypeptides in cerebral cortex. Taken together, chronic ethanol administration produced an upregulation of the beta-subunit mRNA and the polypeptide expression of these subunits in rat cerebral cortex. In contrast, chronic ethanol treatment decreased the expression of various alpha-subunits in the cerebral cortex.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Chronic ethanol treatment upregulates the GABA receptor beta subunit expression. 805 81

Prolonged occupancy of GABAA receptors by ligands, including GABA and benzodiazepine agonists, sets in motion a series of mechanisms that can be termed use-dependent regulation. These mechanisms can be subdivided into two distinct pathways, one for GABAA receptor downregulation and another for upregulation. Treatment of cortical neurons with GABA or benzodiazepines in cultures opens the pathway for GABAA receptor downregulation, which includes (in putative temporal order): (1) desensitization (tachyphylaxis), (2) sequestration (endocytosis) of subunit polypeptides and uncoupling of allosteric interactions between GABA and benzodiazepine binding sites, (3) subunit polypeptide degradation, and (4) repression of subunit gene expression. The end-point of GABAA receptor downregulation, a reduction in receptor number, is postulated to be established initially by degradation of the receptor protein and then maintained by a diminished level of de novo synthesis. Benzodiazepine treatment of many preparations, including cells expressing recombinant GABAA receptors, may elicit only desensitization, sequestration, or uncoupling, without a decline in receptor number. Components of the GABAA receptor downregulation pathway are also evoked by chronic administration of GABAmimetics, benzodiazepines, barbiturates, and neurosteroids in animals. This downregulation correlates with the establishment of tolerance to and physical dependence on the pharmacological effects of these drugs, suggesting a cellular model for this behavior. The upregulation of GABAA receptors is observed as one of the neurotrophic actions of GABA, primarily in cultured cerebellar granule cells. Upregulation in culture is caused by enhanced expression of genes for GABAA receptor subunits and correlates with the establishment of GABAergic circuitry in the developing cerebellum. Thus, both the upregulation and downregulation of GABAA receptors appear to represent use-dependent pathways for guiding synaptic plasticity in the vertebrate central nervous system.
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PMID:Use-dependent regulation of GABAA receptors. 889 44