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)

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

Genetically seizure susceptible DBA/1/Bg mice fed 10% ethanol in their drinking water exhibited a marked diurnal variation in blood alcohol levels. At peak levels, sound-induced seizures were significantly reduced. At trough levels, seizures remained unaffected. Ethanol administered during early development enhanced seizures at post-weaning age. Such alcohol-augmented seizures were suppressed by ethanol feeding during the testing period, to the same base level as in animals not pretreated with ethanol in early life.
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PMID:Suppressant effects of alcohol on audiogenic seizures. 123 99

One of ethanol's actions after acute exposure is anticonvulsant activity whereas withdrawal from chronic ethanol exposure increases convulsant activity. An increase in neuronal transmission in the GABAergic pathways from striatum to the substantia nigra (SN) and a decrease in GABAergic transmission from SN to superior colliculus (SC) both appear to play a major role in inhibiting seizure propagation. If this is the case, then the changes in seizure sensitivity caused by ethanol may be expected to affect GABAergic transmission in opposite ways in SN and SC. We measured the effects of in vitro ethanol on pre- and postsynaptic indices of GABA transmission using SN and SC tissue from both ethanol-naive rats and rats given ethanol in their drinking water for 24 days and then withdrawn for 24 hr, a treatment that decreases seizure latency. While ethanol inhibited 3H-GABA release from slices of SC at low concentrations (20-100 nM), much higher concentrations were required to inhibit release from SN (100-500 mM). In fact, release from SN was increased by low concentrations of ethanol. Ethanol in vitro (20-1000 mM) also inhibited specific binding of 35S-TBPS to the GABAA receptor but this effect was similar in both potency and efficacy in SC and SN. Next, the in vitro effects of ethanol were measured in rats that had consumed an average of 9.8 g ethanol/kg body weight/day and were then withdrawn for 24 hr. Ethanol inhibition of 3H-GABA release from SC was significantly less in ethanol-treated rats compared to controls whereas the inhibitory effect of ethanol was increased in SN from ethanol-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Selective changes in GABAergic transmission in substantia nigra and superior colliculus caused by ethanol and ethanol withdrawal. 131 35

A classical (Mendelian) genetic analysis of responses to ethanol and nicotine was conducted in crosses derived from mouse lines which were selectively bred for differential duration of loss of the righting response (sleep-time) after ethanol. Dose-response curves for these mice, the long- and short-sleep mouse lines, as well as the derived F1, F2 and backcross (F1 x long-sleep and F1 x short-sleep) generations were generated for several measures of nicotine and ethanol sensitivity. Ethanol sensitivity was assessed using the sleep-time measure. Nicotine sensitivity was tested using a battery of behavioral and physiological tests which included measures of seizure activity, respiration rate, acoustic startle response, Y-maze activities (both crossing and rearing activities), heart rate and body temperature. The inheritance of sensitivities to both of these agents appears to be polygenic and inheritance can be explained primarily by additive genetic effects with some epistasis. Sensitivity to the ethanol sleep-time measure was genetically correlated with sensitivity to both nicotine-induced hypothermia and seizures; the correlation was greater between sleep-time and hypothermia. These data indicate that there is overlap in the genetic regulation of sensitivity to both ethanol and nicotine as measured by some, but not all, tests.
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PMID:Classical genetic analyses of responses to nicotine and ethanol in crosses derived from long- and short-sleep mice. 156 Mar 63

Ethanol (EtOH) withdrawal is characterized by a hyperexcitable state that includes anxiety, tremor, muscle rigidity and seizures. The present three experiments examined the effects of EtOH dependence and withdrawal on the acoustic startle response, an easily quantifiable measure of behavioral reactivity to exteroceptive stimuli. Two intensities of startle stimuli, 105 and 120 dB pulses, were presented to rats during chronic EtOH exposure and during EtOH withdrawal. Prepulse inhibition, which is a sensitive measure of sensorimotor gating processes associated with filtering sensory stimulation, was also assessed during chronic EtOH exposure and withdrawal. Prepulse inhibition was induced by the presentation of a weak 80 dB acoustic stimulus 100 ms prior to a 120 dB stimulus pulse. After 14 days of EtOH liquid diet administration the magnitude of responses elicited by 105 and 120 dB startle stimuli was less in ethanol-treated subjects during continued EtOH access than in animals fed a control liquid diet. When EtOH liquid diet treatment was continued for an additional 3-day period and animals were tested 8 h after withdrawal from EtOH, withdrawn animals were more reactive to startle stimuli at both intensities than were animals maintained on the EtOH liquid diet. A time-course experiment with repeated startle testing at 4, 8, and 12 h post-EtOH exposure revealed significant increases in responding to the 105 dB startle intensity at 8 h post-EtOH exposure. The ability of animals to respond to a prepulse stimulus was not affected during chronic EtOH treatment, but was reduced during withdrawal.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Responding to acoustic startle during chronic ethanol intoxication and withdrawal. 157 Mar 82

We have investigated the pharmacological basis of CNS excitation that occurs in association with general anaesthesia in mice. Propofol produced sustained clonic movements during anaesthesia. Methohexitone produced intermittent non-rhythmic jerking during anaesthesia. Ethanol and pentobarbitone produced anaesthesia without associated clonic movements. Doses of all anaesthetic drugs were equipotent. Surface EEG recordings showed paroxysmal discharges consistent with interictal manifestations of cortical seizures with methohexitone or propofol, but not with ethanol or pentobarbitone. Strychnine, a glycine antagonist without effects on the cerebral cortex, and bicuculline, a GABAA antagonist with effects on the cerebral cortex, were used in doses that were equipotent-0.5 log units less than the ED10 for clonic convulsions. Strychnine potentiated both excitatory behaviour and EEG paroxysmal discharges when given with methohexitone or propofol, but not with ethanol or pentobarbitone. Bicuculline did not affect either behaviour or EEG with any of the anaesthetic drugs. Our data show that methohexitone and propofol produced CNS excitation, while pentobarbitone and ethanol did not. We propose that the pharmacological basis of this excitation may be glycine antagonism occurring in subcortical structures.
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PMID:Does glycine antagonism underlie the excitatory effects of methohexitone and propofol? 164 44

The effects of acute administration of ethanol on t-[35S]Butylbiclophosphorothionate (35S-TBPS) binding measured ex vivo in unwashed membrane preparations of rat cerebral cortex were investigated. Ethanol, given i.g., decreased in a dose-related (0.5-4 g/kg) and time-dependent manner the binding of 35S-TBPS. This effect was similar to that induced by the administration of diazepam (0.5-4 mg/kg i.p.). Scatchard plot analysis of this radioligand binding revealed that ethanol, differently from diazepam, decreased the apparent affinity of 35S-TBPS recognition sites whereas it failed to change the density of these binding sites. The effect of ethanol on 35S-TBPS binding could not be reversed by the previous administration to rats of the benzodiazepine receptor antagonist, Ro 15-1788 (ethyl-8-fluoro-5,6-dihydro-5-methyl-6-oxo-4H- imidazo[1,5a][1,4]benzodiazepine-3-carboxylate). Vice versa, the benzodiazepine receptor partial inverse agonist, Ro 15-4513 (ethyl-8-azido-5,6-dihydro-5-methyl-6-oxo-4H- imidazo[1,5a][4,4]benzodiazepine-3-carboxylate) (8 mg/kg i.p.), prevented completely ethanol-induced decrease of 35S-TBPS binding. The ability of Ro 15-4513 to prevent the action of ethanol was shared by the anxiogenic and proconvulsant beta-carboline derivatives, FG 7142 (N-methyl-beta-carboline-3-carboxamide) (12.5 mg/kg i.p.) and ethyl-beta-carboline-3-carboxylate (0.6 mg/kg i.v.), which, per se, enhanced this parameter. Moreover, ethanol (0.5-4 g/kg) was able to reverse the increase of 35S-TBPS binding elicited by the s.c. injection of isoniazid (350 mg/kg) and to clearly attenuate the severity of tonic-clonic seizures produced by this inhibitor of the GABAergic transmission.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Ex vivo binding of t-[35S )butylbicyclophosphorothionate: a biochemical tool to study the pharmacology of ethanol at the gamma-aminobutyric acid-coupled chloride channel. 170 33

Habituation to a test environment following daily exposure for 5 days was examined in three genetically different strains of mice. C57 animals showed significant habituation to the new environment already on the second day. The habituation of NMRI mice was significant on the third day, whereas CBA mice showed no habituation at all during the experimental period. There was no difference between the animal strains in learning capacity in a passive avoidance test, but CBA mice displayed a significant increase in latency in their performance. When tested for sensitivity to the convulsant actions of GABAergic antagonists, picrotoxin produced seizures at lower doses in CBA as compared to NMRI and C57 mice, whereas there was no difference between the strains in the seizure activity produced by the specific GABA receptor antagonist bicuculline. When the animals were tested for sensitivity to ethanol in a horizontal wire test, ethanol (2 g/kg, IP) produced muscle relaxation in CBA mice whereas the performance of NMRI and C57 was not affected. A large dose of ethanol (4 g/kg, IP) produced a significantly longer sleeping time in CBA mice as compared to NMRI and C57 animals. Ethanol-produced hypothermia was, however, similar in all animals. Environment-dependent development of tolerance to ethanol following daily injections of ethanol for 4 days was examined. C57 mice showed the most rapid development of tolerance towards ethanol's hypnotic actions, whereas CBA mice showed no tolerance to this effect of ethanol. No difference between the strains to the development of tolerance to ethanol's hypothermic effects was observed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Evidence that genetic differences in habituation and GABAergic mechanisms may be related to sensitivity to ethanol and development of ethanol tolerance in mice. 174 5

The functional state of GABAA receptors during physical dependence on ethanol was evaluated in two ways. First, the ability of ethanol dependence to change the convulsant potency of GABAA antagonists microinjected into the inferior colliculus was examined. A second approach evaluated the effects of ethanol dependence on the ability of muscimol or pentobarbital to stimulate chloride uptake in rat brain vesicles. In the studies examining changes in convulsant potency, bilateral microinfusions of GABAA antagonists, bicuculline methiodide and picrotoxinin, as well as the excitatory amino acid agonist, kainic acid (used as a positive control) induced similar dose-related increases in the frequency of wild-running seizures. Ethanol dependence did not significantly change susceptibility to wild-running seizure induction by an of the convulsants, although susceptibility to the more severe, clonic seizures was significantly increased for each convulsant. This suggested that the receptor-blocking effects of GABAA antagonists responsible for inducing wild-running seizures were not selectively increased by ethanol dependence, but that spread of seizure activity responsible for clonic seizures following the initiation of wild running was generally increased. Finally, in studies examining changes in GABAA receptor-mediated chloride uptake, both muscimol and pentobarbital were found to induce concentration-dependent increases in chloride uptake in rat brain vesicles. However, responses to these drugs were not reduced by ethanol dependence suggesting that a generalized adaptive decrease in GABAA receptor function was unlikely. Together these results do not provide support for the hypothesis that the GABAA receptor-chloride channel complex is down-regulated during the development of physical dependence on ethanol.
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PMID:Effect of ethanol dependence on GABAA antagonist-induced seizures and agonist-stimulated chloride uptake. 178 22

Unit activity was recorded from the motor cortex of eight freely moving rabbits in order to examine the acute effect of ethanol (1 g kg-1) on organization of unit activity and to compare it with our earlier results from the limbic cortex. The rabbits performed a food-acquisition task in the experimental cage. Unit activity was recorded during behaviour in the control experiment followed by the alcohol experiment on the next day. After ethanol, behavioural mistakes and the duration of the behavioural cycle significantly increased. In the control experiments activation of 58% of the units had no constant relation to the phases of the behavioural cycle (non-involved units), whereas 42% of the units were constantly activated during certain phases (involved units). Two per cent of the latter units were activated in relation to newly learned behavioural acts (e.g. pedal pressing; L units), 28% in relation to food seizure and/or grinding (S units) and 12% in relation to certain movements during different behavioural acts (M units). Ethanol had no effect on the number of active units and the same relation between the number of non-involved and involved units or between the number of different types of involved units was found. However, the number of involved units decreased in the upper and increased in the lower cortical layers. Also the number of units with low background frequency increased, although the frequency within activations did not change. In our earlier study the number of active units in the limbic cortex decreased after ethanol by one third and the relation between the number of L and M units was reversed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Acute effects of alcohol on unit activity in the motor cortex of freely moving rabbits: comparison with the limbic cortex. 192 55


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