Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.1.7 (acetylcholinesterase)
 28,390 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tolerance to and physical dependence on morphine were produced and assessed in Swiss inbred albino mice by giving morphine sulphate (s.c.) three times a day for a period of 15 days in an increasing dose of 10 mg/kg every 24 hours. Physical dependence was assessed taking naloxone induced jumping as well as weight loss during normal withdrawal into consideration. The effect of sodium ions in the potency of naloxone in antagonizing morphine's effect was also analyzed. The spinal cord was assayed for acetylcholinesterase employing both biochemical and histochemical parameters. It was found that the amount of the enzyme increased with the development of tolerance but the amount decreased as the animals became physically dependent. However, the values were significantly above the control. Administration of naloxone brought about a sudden and significant fall in the level of the enzyme. Normal withdrawal too was characterized by a weak activity of the enzyme. It has been found that sodium ions can influence naloxone antagonism in an in vivo system.
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PMID:Fluctuations of acetylcholinesterase in the mouse spinal cord and in vivo sodium effect during the development of morphine tolerance, dependence, and withdrawal. 372 59

A progressive increase in activity of some brain membrane-bound enzymes is shown after 2 and 4 weeks of ethanol administration. After 4 weeks the activities in brain homogenate of (Na+, K+) ATPase, Ca++ ATPase, 5'-nucleotidase, acetylcholinesterase and adenylate cyclase increased 150, 200, 140, 125 and 129 percent, respectively. Arrhenius plots of synaptosomal (Na+, K+) ATPase and acetylcholinesterase from alcohol-treated rats showed a lower transition temperature than control rats after two weeks, and this changed to a higher transition temperature after 4 and 8 weeks. Also, when ethanol was added in vitro to the control membranes, the transition temperature was lowered. However, if the alcohol was added to the membranes from alcohol-treated animals, the transition temperature was lowered to a value similar to that of controls. Fluorescence studies with l-anilinonaphthalene-8-sulfonate (ANS) demonstrate that ethanol induces a decrease in the fluorescence of ANS bound to brain synaptic membranes. This decrease in fluorescence is less than when these membranes are derived from chronically ethanol-treated rats. Also, when the synaptosomal enzymes were exposed to exogenous agents such as detergents, the enzyme obtained from alcohol-treated rats was more stable than that from control rats. These findings indicate a protein conformation change, probably due to the alteration of the physical properties of membrane lipids following chronic ethanol administration. These findings also demonstrate that there is a resistance to the effect of ethanol in membranes of animals habituated to ethanol that may be related to the adaptative modifications that underlie tolerance to and physical dependence on alcohol.
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PMID:Chronic ethanol treatment affects synaptosomal membrane-bound enzymes. 631 83

The distribution of acetylcholinesterase in the brain is studied during the development of morphine tolerance and through a period of withdrawal to elucidate the possible role of this enzyme in producing physical dependence in mice. Tolerance and physical dependence are produced in male albino mice by giving morphine sulphate subcutaneously at eight hourly intervals, in an increasing dose of 10 mg/kg body weight every 24 hours, for 15 days. The animals are considered addicted, when they received an otherwise lethal dose, 150 mg/kg three times a day. The enzyme shows a marked elevation in the overall distribution during the development of physical dependence. The habenular complex, nuclei anterioventralis and medialis thalami, nucleus caudatus putamen, amygdaloideus lateralis, septal nuclei, nucleus nervi hypoglossi, nucleus reticularis lateralis, tuberculum olfactorium, nucleus tractus diagonalis brocae, stratum pyramidale hippocampi, nucleus paraventricularis thalami, nucleus dorsalis nervi vagi, nucleus tractus spinalis nervi trigemini and nucleus reticularis thalami show an increase in the enzyme activity. This enhancement is not linear with the increase in dosage. Withdrawal is characterised by a sudden fall in the activity of acetylcholinesterase in the above mentioned areas of brain.
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PMID:Acetylcholinesterase changes in the central nervous system of mice during the development of morphine tolerance addiction and withdrawal. 668 83

The effects of chronic treatment with morphine and cholinergic compounds on the development of morphine tolerance, physical dependence and increased naloxone potency were studied. Using the abdominal constriction method, it was shown that morphine tolerance was apparent after s.c. administration of morphine 20.0 mg/kg three times a day for four days. It was found that, in animals which showed a low degree of morphine tolerance, the naloxone potency was similar to that determined in mice which had been pretreated with only a single dose of morphine which causes no measurable tolerance. Thus, the development of increased naloxone potency and tolerance to morphine do not parallel each other. In addition, while atropine inhibited, and anti-cholinesterase drugs enhanced, the development of increased naloxone potency caused by morphine treatment they had no or little effect on the development of morphine tolerance. Furthermore, chronic treatment with cholinergic agonists reduced, while muscarinic antagonist enhanced, the development of physical dependence on morphine as assessed by withdrawal jumping and body weight loss. It is concluded that the increased potency of naloxone in antagonising the antinociceptive effect of morphine can be dissociated from the development of tolerance to, and physical dependence on, morphine in mice.
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PMID:The effects of cholinergic compounds on the development of morphine tolerance, dependence and increased naloxone potency in mice. 718 53

Treatment of opiate addiction is generally directed at the suppression of withdrawal symptoms through maintenance of the 'addicted' state with methadone. Yet relatively little is known regarding the neural substrates that contribute to, and maintain the prolonged state of withdrawal experienced by addicts. Opiates can profoundly alter the dynamics of brain and peripheral cholinergic systems, and central administration of anticholinergic drugs in dependent rats has been shown to decrease the expression of precipitated withdrawal symptoms. The purpose of this study was to determine whether the adaptive changes to M2 muscarinic receptors in autonomic centers are linked to the expression of withdrawal phenomena. During the peak period of withdrawal, there was a significant increase in both the expression of M2 muscarinic receptors and its corresponding mRNA within the rostral ventrolateral medulla, a primary vasomotor region. That most of these changes in receptor expression were adaptive in nature was suggested by the fact that when the acetylcholinesterase inhibitor DFP was co-administered with morphine, both the increased mRNA expression and the appearance of withdrawal symptoms were inhibited. Thus, interference with morphine-induced M2 muscarinic receptor adaptation in critical brain regions was correlated with a reduction in the development of physical dependence.
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PMID:Prevention of morphine-induced muscarinic (M2) receptor adaptation suppresses the expression of withdrawal symptoms. 972 19

Previous studies in this and other laboratories have suggested an important role for central cholinergic neurons in the expression of morphine withdrawal symptoms. This study was designed to determine whether the symptoms of withdrawal could be mitigated by normalization of the effect of morphine on cholinergic neurons. Since this effect is generally inhibitory, we used centrally acting cholinergic agonists to augment central cholinergic tone during chronic morphine infusion. Rats were made dependent following the intra-arterial (i.a.) infusion of increasing concentrations (35-100 mg kg(-1) day(-1)) of morphine over 5 days. I.a. injection of 0.5 mg/kg of naloxone precipitated a profound withdrawal response that included a dramatic increase in mean arterial pressure (MAP) which was maintained over the 60-min observation period, a short duration increase in heart rate (HR), and characteristic opiate withdrawal symptoms. In separate groups of rats, non-toxic doses (50 and 250 microg/kg) of the acetylcholinesterase (AChE) inhibitor, diisopropylflurophosphate (DFP) were administered as single daily injections concomitant with the morphine infusion. DFP treated rats, exhibited significantly reduced expression of the naloxone-evoked pressor response. The apparent anti-withdrawal effect of DFP was not reproduced by the selective peripherally acting AChE inhibitor, echothiophate, although both compounds effectively reduced the expression of certain other withdrawal symptoms. The centrally acting muscarinic cholinergic receptor agonist, arecoline, resulted in an even more impressive suppression of withdrawal symptoms. While not all symptoms associated with morphine withdrawal are mediated via central cholinergic pathways, these results suggest that physical dependence on morphine can be suppressed to a significant degree by the augmentation of central cholinergic activity during morphine administration.
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PMID:Prevention of precipitated withdrawal symptoms by activating central cholinergic systems during a dependence-producing schedule of morphine in rats. 1066 98