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

Bovine adrenal chromaffin cells were dissociated and grown in primary culture for 9 days. Three days after plating, half the cultures were grown in a medium containing 200 mM ethanol and the other half in a control medium, for a further 6 days. The catecholamine content of the ethanol-treated cells was increased after 6 days of ethanol treatment, compared to control cells and there was a slight reduction in protein and DNA content. An enhanced spontaneous release of catecholamines was seen, which was Ca(2+)-dependent and was inhibited by cadmium but not by the organic dihydropyridine Ca2+ antagonist nitrendipine. The fraction of catecholamines released by K+ was also enhanced in ethanol-treated preparations, particularly at high K+ or Ca2+ concentrations. Release induced by K+ was sensitive to inhibition by both cadmium and organic dihydropyridine Ca2+ antagonists. The results show many similarities with changes observed in catecholaminergic transmission in rat brain during the development of ethanol physical dependence.
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PMID:Characteristics of catecholamine release from adrenal chromaffin cells cultured in medium containing ethanol--I. Spontaneous and K(+)-induced release. 164 7

Ethanol physical dependence can be viewed as a state of latent hyperexcitability in brain which is exposed on withdrawal of the drug. This hyperexcitability may reflect an increased sensitivity to Ca2+ of central neurones. Dihydropyridine (DHP) binding sites which represent a subtype of neuronal Ca2+-channel, are increased in brains from ethanol-dependent rats as are functional effects of the DHP Ca2+-channel activator, BAYK8644. These effects are reversed by DHP Ca2+ inhibitors, which also prevent the ethanol physical withdrawal syndrome. These results suggest that an increase in DHP-sensitive Ca2+-channels on central neurons may represent the molecular basis for ethanol physical dependence.
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PMID:Increased dihydropyridine-sensitive calcium channels in rat brain may underlie ethanol physical dependence. 243 83

Studies with ethanol have indicated that dihydropyridine-sensitive calcium (Ca++) channels may be involved in the adaptation to prolonged exposure to ethanol. This study investigated the effects, in mice, of the dihydropyridine Ca++ antagonist, nitrendipine, on acute tolerance to nitrous oxide after 60 min exposure to anesthetizing concentrations, and also the withdrawal syndrome which occurred following removal from nitrous oxide. Control mice were anesthetized by nitrous oxide concentrations in the range 1.28-1.51 atmospheres. Nitrendipine 10, 50, and 100 mg.kg-1, i.p., produced a dose-dependent potentiation of nitrous oxide anesthesia (P less than 0.05 for nitrendipine 50 and 100 mg.kg-1). Tolerance to nitrous oxide anesthesia developed over 60 min (13% increase in ED50, P less than 0.05). Concurrent administration of nitrendipine at all doses prevented the development of nitrous oxide tolerance. After 60 min exposure to nitrous oxide 1-1.5 atmospheres, all control mice showed handling seizures. Nitrendipine diminished or prevented nitrous oxide withdrawal seizures, in a dose-dependent manner (P less than 0.05 for nitrendipine 50 and 100 mg.kg-1). These results support the importance of the role of dihydropyridine-sensitive Ca++ channels in the mechanism of tolerance and dependence to central depressant drugs. They also suggest that acute and chronic tolerance to sedative drug action may share some common pathways, and that tolerance and physical dependence may share a common mechanism through voltage-operated Ca++ channels.
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PMID:Effects of "nitrendipine" on nitrous oxide anesthesia, tolerance, and physical dependence. 252 37

The calcium antagonists nimodipine and dantrolene were compared with diazepam in an animal model of tolerance and physical dependence upon ethanol. Nimodipine and dantrolene were both effective in suppressing withdrawal tremors but diazepam was clearly superior to both agents. These results suggest that the ethanol withdrawal syndrome is only partially mediated by increased calcium flux.
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PMID:A comparison of calcium antagonists and diazepam in reducing ethanol withdrawal tremors. 259 4

Clinically, patients with Delirium Tremens (DT) and acute alcohol hallucinosis (impending DT) appear excited with vivid false perception. Cerebral blood flow and eeg correspondingly point to hyperexcitability in the CNS during these conditions. Clinical trials with barbital treatment in alcohol withdrawal shows that the amount of drug and the drug plasma concentration is the same no matter whether the physical signs of withdrawal are accompanied by hallucinations and clouding of consciousness. The psychotic signs in DT and acute alcoholic hallucinosis develops after many years of alcoholism as does seizures. We hypothesize that physical withdrawal is determined by the degree of physical dependence developed during the most recent drinking period whereas the psychotic signs and seizures are due to a cumulated CNS hyperactivity developed over many years of repeated alcohol intoxication and withdrawal. Changes of electrolyte concentrations in plasma or CSF do not play an important role in the pathogenesis of DT and related clinical states except that changes in calcium and inorganic phosphate metabolism indirectly point to changes in membrane excitability. A new model for a study of rapidly repeated intoxication and withdrawal episodes in rats has shown that repetition of episodes augments the convulsive component of withdrawal whereas the non-convulsive signs are dependent on the most recent episode only. The augmentation of the convulsive component correlates with regional differences in brain glucose consumption. Furthermore, synaptic proteins and acidic phospholipids may be involved in the development of CNS hyperexcitability during alcohol withdrawal. In conclusion both clinical and experimental studies indicate that severe alcohol withdrawal reactions may consist of two components: 1) Physical withdrawal signs determined by recent physical dependence. 2) A long term cumulated CNS hyperexcitability relating to seizures and psychotic signs during withdrawal. This state is elicited by alcohol withdrawal but it represents a cumulated and permanent or long lasting CNS dysfunction in alcoholics. The precise biochemical/pathophysiological mechanisms for the development of the two-component dysfunction still remain to be clarified in detail.
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PMID:Delirium tremens and related clinical states: psychopathology, cerebral pathophysiology and psychochemistry: a two-component hypothesis concerning etiology and pathogenesis. 306 44

In synaptosomal fractions of rat brain the activities of phospholipase A2 and the phospholipid base-exchange enzymes are highly dependent on external Ca2+ concentrations. Their activity is inhibited by the presence of 50 mM ethanol in vitro. Administration of ethanol to rats by inhalation causes a progressive increase in the activity of these enzymes in synaptosomal preparations at all Ca2+ concentrations studied. The increased activity of these enzymes persists in preparations from rats undergoing a physical syndrome of withdrawal from ethanol. The addition of ethanol in vitro to preparations from animals that had received ethanol in vivo had no significant effect on enzyme activity. The results are discussed in relation to the possible roles of membrane lipid metabolism and synaptic Ca2+ sensitivity in ethanol tolerance and physical dependence.
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PMID:Increased activity of Ca2+-dependent enzymes of membrane lipid metabolism in synaptosomal preparations from ethanol-dependent rats. 391 59

The effects of taurine on the analgesic response to morphine, on the intensity of tolerance and on physical dependence were examined. Taurine induced a hyperalgesic state and attenuated morphine analgesia in mice. The hyperalgesia was maximal at a dose level of 1.5 mg/kg i.p., while the effects of higher doses (6.0 and 10.0 mg/kg) were masked by a depression of the animals' gross behavior. Taurine induced a dose related antagonism of morphine tolerance. The amino acid administered 30 min before naloxone, produced a partial reduction in the abstinence signs in the chronically treated mice. Taurine also attenuated the abstinence behavior when administered during the course of dependence. The results are consistent with taurine antagonism to the known effects of morphine on intracellular calcium disposition in nervous tissue.
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PMID:Effects of taurine on tolerance to and dependence on morphine in mice. 653 78

Effects of morphine on calcium uptake into synaptosomes isolated from acutely or chronically morphine-tolerant rat brain was studied. Addition of morphine inhibited the depolarization-stimulated uptake of calcium without affecting uptake under nondepolarizing conditions. This inhibition was prevented by simultaneous addition of naloxone with morphine before calcium uptake was initiated. Acute tolerance to morphine increased depolarization-stimulated synaptosomal calcium uptake. On the other hand, chronic exposure of rats to morphine to elicit tolerance to and physical dependence on morphine did not influence synaptosomal calcium uptake. However, these preparations apparently lost the ability of in vitro morphine-inhibition of calcium uptake into the synaptosomes. Our results suggested that adaptive changes of synaptosomal calcium uptake produced by exposure to morphine may be involved in tolerance and physical dependence development, but influence of morphine on calcium uptake by the synaptosomes isolated from the rats acutely tolerance to morphine was differed from that of chronic tolerant rats.
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PMID:Effect of morphine on the stimuli-induced calcium uptake into synaptosomes isolated from morphine-tolerant rats. 713 49

The influence of an L-type Ca2+ channel blocker, diltiazem [(2S-cis)-3-(acetyloxy)-5-[2-(dimethylamino)-ethyl]-2,3-dihydro-2- (4- methoxyphenyl)-1,5-benzothiazepin-4(5H)-one], on the behavioral signs of naloxone (opioid receptor antagonist)-precipitated withdrawal syndrome and the enhancement of protein kinase C activity in the pons/medulla regions of rats rendered dependent on morphine (mu-opioid receptor agonist) or butorphanol (mu/delta/kappa mixed opioid receptor agonist) was investigated. The expression of physical dependence produced by continuous intracerebroventricular (i.c.v.) infusion of morphine (26 nmol/microliters per h) or butorphanol (26 nmol/microliters per h) for 3 days, as evaluated by naloxone (5 mg/kg, i.p.)-precipitated withdrawal signs, was dose dependently attenuated by concomitant infusion of diltiazem (10 and 100 nmol/microliters per h). Furthermore, diltiazem (100 nmol/microliters per h) completely inhibited the enhancement of cytosolic protein kinase C activity in the pons/medulla regions in rats rendered dependent by continuous infusion with morphine or butorphanol. These results suggest that the augmentation of intracellular Ca2+ concentration mediated through L-type Ca2+ channels during continuous opioid infusion leads to the enhancement of cytosolic protein kinase C activity in the pons/medulla region which is intimately involved in the development and/or expression of physical dependence on opioids.
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PMID:Ca2+ channel blocker, diltiazem, prevents physical dependence and the enhancement of protein kinase C activity by opioid infusion in rats. 755 88

Prolonged ethanol administration causes upregulation of dihydropyridine-sensitive binding sites, thought to represent neuronal calcium channels, and these channels appear to play an important role in ethanol physical dependence. Dihydropyridine calcium channel antagonists, when given chronically with ethanol, prevent the development of tolerance to ethanol and the ethanol withdrawal syndrome. The upregulation of binding sites for these compounds was also prevented. Epileptiform activity has been described in isolated hippocampal slices after chronic ethanol treatment in vivo. This was prevented, stereoselectively, by the dihydropyridine calcium channel antagonist, isradipine, that did not affect the hyperexcitability produced in control slices by the GABAA antagonist, bicuculline.
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PMID:Calcium channel antagonists prevent adaptive responses to ethanol. 774 8


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