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)

A new type of morphine implantation pellet for the rapid induction of physical dependence in mice can be prepared by absorbing 7 mg morphine sulphate onto molecular sieves Type 4A (BDH). The small cylindrical pellets can be implanted subcutaneously without trauma and the need for anaesthesia, and are easily removed at any time from the animals. The peak of physical dependence is reached 24 h after implantation, and mortality is negligible. Withdrawal symptoms can be precipitated by intraperitoneal injection of naloxone, without removal of the pellet, and up to 70% of a group of mice show the characteristic urge to jump off a raised platform. This type of pellet has definite advantages over some other sustained-release preparations used in studies on morphine addiction in small animals.
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PMID:An improved implantation pellet for rapid induction of morphine dependence in mice. 23 71

ICR male mice each receiving a 16 mg barbital pellet implanted subcutaneously for three days developed about 40 percent tolerance to barbital and more than 50 percent tolerance to pentobarbital as measured by sleeping time. The development of physical dependence in these mice was demonstrated by an increased sensitivity to convulsions with pentylenetetrazol. The concentration of barbital rose to high levels in the subcortex and the cerebellum during the time between the implantation of the pellet and the loss of the righting reflex and distributed uniformly thereafter. After a challenge dose of the drug, higher barbital concentrations were found in these two areas as well as in the pons-medulla at 30 minutes and in all areas at the time of the loss of righting reflex, in withdrawn mice. The latter finding would indicate an increase in threshold for barbital anesthesia. The mechanisms of the higher uptake in the brain of withdrawn mice are discussed.
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PMID:Regional distribution of barbital in the brain of mice during the development of tolerance and physical dependence. 56 25

3 experimental approaches to the quantitation of acute barbiturate tolerance have been compared in the rat. There was no difference between the brain hexobarbitone or barbitone concentration found at the time of loss of righting reflex compared with the concentration found on return of the righting reflex following the period of anaesthesia produced by a single i.p. injection of the drug. However, tolerance was induced by a 7 hr infusion of pentobarbitone which kept rats anaesthetized for approximately 8 hr. Such rats awakened with a significantly higher brain pentobarbitone concentration compared with rats awakening after a single i.p. injection. Repeated i.p. injections of pentobarbitone, sufficient to keep animals anaesthetized for 12 hr, also induced a tolerance to pentobarbitone, as indicated by a reduced sleeping time and higher brain barbiturate concentration on awakening following intracerebroventricularly administered pentobarbitone injected 12 hr after the last i.p. injection. The possible relationship between acute cellular tolerance and physical dependence is discussed.
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PMID:Acute tolerance to barbiturate in the rat. 94 31

Cats were made physically dependent on sodium pentobarbital using the "maximally tolerable" dosing technique. All animals treated this way receive equieffective doses chronically and all become severly dependent. After 5 weeks of treatment each cat displayed withdrawal signs indicative of severe physical dependence. At specific times after the last dose, electrophysiological measurements of spinal cord segmental reflex function were made. Under brief volatile anesthesia, a C1 spinal section was performed. The lumbar spinal cord was exposed by laminectomy and a hindleg was dissected to provide peripheral nerves for stimulation. Recordings were taken from ventral roots L7 and S1 that had been cut near their exits through the dura. Following single, supramaximal sciatic nerve shocks, monosynaptic (2N) responses were not altered during withdrawal, but both the amplitude and duration of polysynaptic response and of afterdischarge were increased withdrawing cats. The rate of 2N synaptic recovery, measured by a paired stimuli technique, was found to be increased during withdrawal. The 2N pathway was able to transmit more effectively during repetitive stimulation since there was less decrement in response during transmission. The relationship between post-tetanic potentiation and tetanic frequency was shifted toward lower frequencies. The size of the motor neuron pool, estimated by maximum post-tetanic potentiation, and the 2N discharge zone were not altered. Background discharge ("noise") was increased during withdrawal.
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PMID:Electrophysiology of barbiturate withdrawal in the spinal cord. 98 77

In previous studies, development of functional tolerance to the anticonvulsant effect of clonazepam and physical dependence on the drug have been demonstrated. In the present study, dogs were treated for 6 weeks with clonazepam 0.5 mg/kg b.i.d. Under methohexital anesthesia, cerebrospinal fluid samples were taken before treatment, at 3 days (acute effect), 4 and 5 weeks (tolerance) after the start of treatment, 2 and 8 days after withdrawal and 5 weeks after the end of treatment as another control. The following transmitters or metabolites were determined: HVA, VMA, 5-HIAA, GABA, PGE2, TXB2 and 6-keto PGF1 alpha. 5-HIAA levels showed a significant rise, indicating an increased activity of the serotonergic system in the brain during development both of tolerance and withdrawal. Dopaminergic activity was not altered during treatment, but was increased after cessation of treatment, as indicated by a significant increase in HVA concentrations.
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PMID:Metabolism of central neurotransmitters during development of tolerance to the anticonvulsant effect of clonazepam and of physical dependence on the drug in dogs. 170 Jun 84

The effect of morphine tolerance-dependence and abstinence on dopamine D1 receptors in brain regions and spinal cord was determined in rats. Male Sprague-Dawley rats were implanted s.c. under light ether anesthesia with 6 morphine pellets, each containing 75 mg of morphine free base. Rats serving as controls were implanted with placebo pellets. This procedure resulted in the development of tolerance to morphine as evidenced by decreased analgesic response to a challenge dose of morphine. Similarly, the development of physical dependence was evidenced by decreased body weight and colonic temperature after morphine pellet removal (withdrawal). Two sets of animals were used for receptor binding studies. In one, the pellets were left intact and in the other, the pellets were removed. Eighteen hours after pellet removal, the rats were sacrificed. [3H]SCH 23390 [( R-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1-3-benzapine- 7-ol]) bound to brain region and spinal cord membranes of placebo pellet-implanted rats at a single high affinity site. In rats treated chronically with morphine and then withdrawn, the binding of [3H]SCH 23390 to membranes of spinal cord, hypothalamus and striatum was increased but the binding to amygdalar membranes was decreased in comparison with placebo-treated rats. The changes in binding were due to the changes in Bmax values; the Kd values were unaffected. The behavioral responses to a selective dopamine D1 receptor agonist, SKF 38393 [( 1-phenyl-2,3,4,5-tetrahydro (1H)-3-benzapine-7,8-diol hydrochloride]), were also enhanced in morphine-withdrawn rats when compared to placebo controls.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Modification of brain and spinal cord dopamine D1 receptors labeled with [3H]SCH 23390 after morphine withdrawal from tolerant and physically dependent rats. 213 69

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

A study was made of the density and affinity of benzodiazepine receptors in the cortex of the cerebral hemispheres and hippocampus of rats with different predisposition to alcohol consumption. No differences were revealed in the parameters under study in animals with varying duration of ethanol anesthesia and in rats after voluntary consumption of ethanol for 3.5 and 10 months. In a state of abstinence rats with physical dependence manifested a dramatic decrease in the density and affinity of benzodiazepine receptors in the cortex of the cerebral hemispheres. No changes described were detected in the hippocampus. The role of benzodiazepine receptors in the development of abstinence is discussed.
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PMID:[Characteristics of the benzodiazepine receptors in rats with different predispositions to the development of experimental alcoholism]. 299 77

The concentration of beta-endorphin was determined in the cortex of the large hemispheres, thalamus, striatum and medulla oblongata of rats with varying duration of ethanol anesthesia and after a single injection of ethanol (2.5 g/kg). The content of beta-endorphin was also measured in the brain of rats which preferred and rejected 15% ethanol during long-term (up to 10 months) alcoholization. The data obtained indicate that ethanol produces a specific effect on the endorphinergic system in different brain structures of animals predisposed to voluntary alcoholization. A possible involvement of the neuropeptide in the formation of alcohol tolerance and physical dependence is discussed.
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PMID:[Effect of one-time and chronic administration of ethanol on the concentration of beta-endorphin in the brain of rats with different alcoholic motivation]. 630 22

Mice may be induced to convulse after (but not prior to) breathing nitrous oxide. We found that the incidence of this withdrawal phenomenon is related to the partial pressure of nitrous oxide. A minimum (threshold) value of about 0.5 atm is necessary and the majority of mice convulse following exposure to 0.9 atm or greater. Exposures of longer than 15 to 30 minutes do not significantly increase the incidence of convulsions at any given partial pressure. The mice remain susceptible to the induction of convulsions for only a brief period after removal from nitrous oxide. Although the duration of susceptibility is slightly increased after exposure to higher partial pressures, susceptibility in almost all cases is lost by 90 minutes. In mice, exposure to nitrous oxide is associated with evidence of physical dependence as evidenced by withdrawal symptoms, symptoms that be related to the appearance of excitement which sometimes follows nitrous oxide anesthesia.
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PMID:Withdrawal convulsions in mice following nitrous oxide. 718 61


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