Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The i.v. pentylenetetrazol seizure threshold was increased by 2.5 mg/kg and decreased by 15 mg/kg of a single (+)-amphetamine dose. After 7 consecutive days of amphetamine administration, tolerance developed to the decrease but not to the increase in seizure threshold. At 12--48 h after the last dose of 2.5 mg/kg seizure threshold was decreased, and at 36--48 h after the last dose of 15 mg/kg seizure threshold was increased. After acute and chronic administration of (+)-amphetamine (2.5 mg/kg) endogenous concentrations of whole brain dopamine (DA) were increased and returned to normal levels during the withdrawal period (12--48 h); endogenous norepinephrine (NE) levels were unchanged by acute and chronic drug treatment and during withdrawal. The rates of DA and NE synthesis were increased by chronic amphetamine administration at 24--48 h after drug withdrawal. An acute dose of (+)-amphetamine (15 mg/kg) decreased endogenous levels of DA and NE; normal levels of DA were detected with chronic drug treatment and during withdrawal, with NE remaining slightly depressed. The rates of synthesis of DA and NE were increased by acute and chronic amphetamine treatment and returned to normal 24--48 h after withdrawal. The rebound reversal in seizure threshold after (+)-amphetamine withdrawal suggests an abstinence syndrome that may be interpreted as evidence for the development of physical dependence to (+)-amphetamine after chronic drug administration.
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PMID:The effects of chronic administration and withdrawal of (+)-amphetamine on seizure threshold and endogenous catecholamine concentrations and their rates of biosynthesis in mice. 40 70

Infant rats, treated intracisternally with 6-hydroxydopamine or 5,7-dihydroxytryptamine, alone or in combination with desmethylimipramine or pargyline, at 5 to 7 days of age, had significant specific depletions of brain norepinephrine, dopamine, both of these amines, or serotonin at 2.5 months of age. Despite apparent long-term depletions of brain biogenic amines, susceptibility to audiogenically-induced seizures following chronic ethanol withdrawal in these animals was similar to that of controls. Amine-depleted rats also displayed spontaneous withdrawal-induced tremors, spastic motor activity and irritability. The interpretation of these preliminary findings with regard to the proposed role of the biogenic amines in the development of physical dependence on ethanol is discussed.
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PMID:Effects of 6-hydroxydopamine or 5,7-dihydroxy-tryptamine on the development of physical dependence on ethanol. 56 50

Intravenous infusions were used to produce physical dependence upon ethanol in rats. The procedure proved to be safe, rapid, and reliable. Ethanol (30% v/v) was administered over a 7-day period. The mean daily dose ranged from 10--14 g/kg/day. Control rats were exposed to a comparable procedure except that saline, rather than ethanol, was infused. All ethanol treated rats that survived the intoxication period (n = 11) showed signs of physical dependence (moderate to severe, n = 8; mild, n = 3) following ethanol withdrawal. Saline treated rats (n = 8) did not show any of these symptoms. The most reliable ethanol withdrawal signs observed were: spontaneous seizure (n = 7), audiogenic seizure (n = 7), tremors (n = 6), tail stiffening (n = 10) and body rigidity (n = 9). These symptoms were analyzed in terms of their hour of onset and hour of maximum intensity following ethanol withdrawal. Application of the intravenous method for the study of ethanol self-administration is discussed.
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PMID:Induction of physical dependence upon ethanol in rats using intravenous infusion. 56 3

The antiepileptic and prophylactic effects of delta9-tetrahydrocannabinol (delta9-THC) and delta8-THC were examined in rats that developed generalized seizures in response to intermittent electrical stimulation of the amygdala (kindling). Both isomers of the THC were able to acutely suppress kindled seizures, but consistent antiepileptic effects were obtained only with high, toxic dosages. Tolerance to the antiepileptic effects of THC developed very rapidly when the drugs were give repeatedly, and there was evidence that the repeated administration of a high dosage of delta9-THC resulted in a state of acute physical dependence. Administration of the isomers of THC during seizure development resulted in a suppression of kindling, suggestive of a prophylactic effect. The rate of rekindling after withdrawal of the drugs was not significantly different from that of vehicle-treated control rats, however, indicating that a genuine prophylactic effect was not obtained.
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PMID:Antiepileptic and prophylactic effects of tetrahydrocannabinols in amygdaloid kindled rats. 62 68

Rats were treated by intragastric intubation of a 20% ethanol solution in doses of 9-15 g/kg in 3-5 fractions for 1-7 days. Both tolerance and physical dependence were demonstrated after this treatment with the maximum tolerable doses to only a few days. Tolerance was assessed by signs of severity of intoxication: coma, loss of righting reflex, ataxia-3, ataxia-2, ataxia-1, sedation, and neutrality. During withdrawal, as blood ethanol concentrations approached 100 mg/dl the ethanol dependence phase was characterized by the onset of signs and responses of progressive severity: hyperactivity, tremors, spastic rigidity, and spontaneous convulsive seizures. A significant degree of tolerance was demonstrated for all signs of intoxication after 4 days of treatment, but did not reach maximum level even after 7 days. The severity of the withdrawal reactions intensified progressively to a maximum intensity after 4 days of treatment when as many as 72% of animals exhibited severe withdrawal signs and reactions including convulsive seizures. These different time courses suggest that tolerance and physical dependence are mediated through different mechanisms.
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PMID:Temporal relationship of the induction of tolerance and physical dependence after continuous intoxication with maximum tolerable doses of ethanol in rats. 82 49

1 Morphine (1-200 mg/kg s.c.) reduced the incidence and prolonged the latency of priming-induced audiogenic siezures in a dose-dependent manner. 2 This effect was reversed by naloxone (1 and 2 mg/kg) although naloxone was itself inactive. 3 This priming-induces seizure model may be useful in the study of tolerance and physical dependence.
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PMID:Effect of morphine and naloxone on priming-induced audiogenic seizures in BALB/c mice. 100 Jan 29

This study reproduces in experimental animals the sequential development of all the liver lesions seen in the human alcoholic: in 15 baboons fed ethanol, all developed fatty liver, five progressed to hepatitis, and five had cirrhosis. Maintenance of a nutritionally adequate regimen despite the intake of inebriating amounts of ethanol (50% of total calories) was achieved by incorporation of the ethanol in a totally liquid diet. Upon ethanol withdrawal, signs of physical dependence, such as seizures and tremors, developed. Ultrastructural changes of the mitochondria and the endoplasmic reticulum were already present at the fatty liver stage and persisted throughout the hepatitis and cirrhosis. The lesions were similar to those observed in alcoholics (including the inflammation and the central sclerosis) and differed from the alterations produced by choline and protein defiencies. At the fatty liver stage, some "adaptive" increases in activity of microsomal enzymes [aniline hydroxylase (EC 1.14.14.1) and the microsomal ethanol oxidizing system] were observed, but these tended to disappear with the development of hepatitis and cirrhosis. Fat accumulation was also much more pronounced in the animals with the hepatitis as compared with those with simple fatty liver (an 18-fold compared with 3- to 4-fold increase in liver triglycerides). The demonstration that these lesions can develop despite an adequate diet indicates that in addition to correction of the nutritional status, control of alcohol intake is mandatory for the management of patients with alcoholic liver injury.
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PMID:Sequential production of fatty liver, hepatitis, and cirrhosis in sub-human primates fed ethanol with adequate diets. 105 27

Although it has not yet been possible to construct a complete model of alcoholism in experimental animals; some aspects of the disease can now be studied with satisfactory laboratory systems. Production of physical dependence requires a period of continuous intoxication; brief intervals of sobriety allow the accrued dependence to disappear. Administration of ethanol by inhalation, with daily injections of pyrazole, allows maintenance of stable blood alcohol levels in mice. In this model, physical dependence arises to its maximum in a week or two and can decay in less than a day. Sedative drugs suppress the mouse withdrawal reactions but drugs that intefere with catecholamine or gamma-aminobutyric acid pathways facilitate withdrawal seizures. Susceptibility to withdrawal seizures is controlled in part by genetic factors.
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PMID:Physical dependence on alcohol in mice. 109 38

When mice were kept continuously intoxicated by inhalation of ethanol, physical dependence developed progressively, reaching its maximum in about 2 weeks. Decay of physical dependence during periods of sobriety was complete in about a day. These rapid time courses are consistent with a theoretical model in which alcohol inhibits and simultaneously stabilizes its target. This target may be located in central adrenergic synapses, because interference with function of such synapses facilitated the alcohol withdrawal reaction and because strain differences in withdrawal seizure scores correlated well with strain differences in reserpine effects.
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PMID:Drug dependence as an adaptive response: studies with ethanol in mice. 117 82

Rats received intragastric intubations of ethanol at 8 hr intervals for 1, 7, 15 or 30 days. The dosage for each animal was one which produced observable signs of intoxication 1 hr after the intubation. All of the rats in the experimental groups developed a tolerance to ethanol as indicated by the increasing dose required to induce intoxication, but the degree of tolerance was related to the duration of the ethanol administration. During the withdrawal period the incidence of hyperreactivity, convulsive symptoms, and the susceptibility to audiogenic seizures was determined for all 4 groups. Although every experimental animal displayed withdrawal symptoms, the incidence of these symptoms was found to be an increasing, negatively accelerated function of the duration of ethanol exposure. For situations where voluntary consumption of alcohol is not necessary this method is a simple, controlled, reliable, way of inducing ethanol tolerance and physical dependence in rats.
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PMID:Simple method for producing an alcohol withdrawal syndrome in rats. 123 71


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