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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of four neural excitants (damphetamine, cocaine, nicotine, and strychnine) on myoclonic and clonic seizure susceptibility were investigated in two age groups (30 and 120 days) of short-sleep mice. Amphetamine and cocaine decreased susceptibility to myoclonus in young mice and increased susceptibility in mature mice. These effects were attenuated by pretreatment with haloperidol, indicating mediation by a dopaminergic system. Amphetamine did not alter clonic susceptibility in either age group of mice, whereas cocaine affected clonic susceptibility and myoclonus. These effects were not attenuated by haloperidol, indicating mediation by systems other than dopamine. Nicotine decreased susceptibility to myoclonus and increased susceptibility to clonus, whereas strychnine increased susceptibility to both types of seizure. Haloperidol, however, failed to alter any of these effects. These results are consistent with our previous work which suggests that a dopaminergic mechanism in these mice undergoes marked developmental changes between 30 and 120 days of age.
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PMID:Maturational changes related to dopamine in the effects of d-amphetamine, cocaine, nicotine, and strychnine on seizure susceptibility. 11 67

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

Acetylcholine activates both nicotinic and muscarinic receptors in the central nervous system. Although the action of acetylcholine at muscarinic receptor has been well characterized, relatively little is known at the cellular level concerning nicotinic receptor stimulation in brain. Central nicotinic receptors have been implicated in Alzheimer's disease, seizure activity, the generation of slow-wave theta rhythm in the hippocampus and the potential abuse liability of nicotine. At the neuronal level, nicotinic agonists have been most often associated with postsynaptically mediated excitation and membrane depolarization at various sites, including Renshaw spinal motoneurons, locus coeruleus and the medial habenular nucleus. Nicotine acting presynaptically can produce either excitation or inhibition indirectly through the release of endogeneous transmitters or modulators. Whereas a direct inhibitory effect of nicotine has been suggested by one in vivo extracellular recording study in rat cerebellar Purkinje neurons, the mechanism(s) underlying this action is not yet known. We now report our findings obtained using in vitro intracellular methods in a submerged brain slice preparation in which application of nicotinic agonists to rat dorsolateral septal neurons reveal a direct membrane hyperpolarization mediated by an increase in potassium conductance.
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PMID:A direct nicotinic receptor-mediated inhibition recorded intracellularly in vitro. 279 67

Nicotine-induced seizure sensitivity was assessed in 19 inbred mouse strains. Two routes of drug administration were utilized: acute intravenous (IV) infusion and intraperitoneal (IP) injection. Dose-response curves for sensitivity to IP nicotine-induced seizures were constructed for the 19 inbred strains and a heterogeneous stock (HS/Ibg) of mice. Differences were observed among the strains both in ED50 values and slopes of the dose-response curves following IP injection of nicotine. ST/bJ mice were the most sensitive having an ED50 of 2.34 +/- 0.09 mg/kg nicotine. DBA/1J mice were the most resistant strain with an ED50 value of 6.16 +/- 0.02 m/kg nicotine. Latency to clonic seizure was measured in the 19 inbred mouse strains using the acute IV route of drug administration. Again, ST/bJ mice were the most sensitive and DBA/2Ibg were the most resistant to IV nicotine-induced seizures. Significant correlations were observed between latency to IV nicotine-induced seizures and both ED50 values and the slope of the dose-response curves for IP nicotine-induced seizures. However, the pattern of results differed between the two routes of drug administration. The relationship between seizure sensitivity and nicotinic receptor concentration in three brain regions, cortex, midbrain and hippocampus, was also assessed using alpha-bungarotoxin (BTX) as the ligand. A significant relationship was observed between BTX binding in the three brain regions and sensitivity to IV nicotine-induced seizures such that strains with greater concentrations of BTX binding sites were more sensitive to nicotine-induced seizures than were strains with lower concentrations of BTX binding sites.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Strain comparison of nicotine-induced seizure sensitivity and nicotinic receptors. 281 85

The effects of nicotine on secretion of the pituitary peptides beta-endorphin, alpha MSH, and ACTH were studied using the isolated perfused mouse brain (IPMB) and isolated superfused pituitaries of C3H mice. Nicotine (6.1 microM) stimulated secretion of beta-endorphin immunoreactivity from C3H IPMB approximately twofold. Secretion of alpha MSH immunoreactivity was stimulated approximately two- and sixfold by 6.1 microM and 12.2 microM nicotine, respectively. However, nicotine (6.1 microM) had no direct effect on the secretion of beta-endorphin, alpha MSH, or ACTH immunoreactivities from the isolated superfused pituitaries. The data suggest nicotine acts in the brain to stimulate pituitary secretion of alpha MSH and beta-endorphin. Electrocorticographic (ECoG) activity of the IPMB was monitored. Nicotine induced characteristic ECoG changes including a reduction of input voltage, a biphasic response of rapid desynchronization followed by prolonged synchronization, and seizure at high doses (12.2 microM).
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PMID:Effects of nicotine on beta-endorphin, alpha MSH, and ACTH secretion by isolated perfused mouse brains and pituitary glands, in vitro. 298 5

Nineteen inbred mouse strains were tested for their relative sensitivity to nicotine's effects on respiratory rate, acoustic startle response, heart rate, Y-maze activity (crosses and rears) and body temperature. Separate animals were tested for their sensitivity to nicotine-induced seizures following IP injection or IV infusion. Dose-response curves were constructed for each measure. Large strain differences were obtained for all of these measures. Nicotine's effects on heart rate, Y-maze activity and body temperature segregated together into the various mouse strains whereas seizure sensitivity segregated independently which suggests that these responses are under separate genetic control. Evidence was obtained which suggests that nicotine-induced seizures are regulated, in part, by the number of hippocampal nicotinic receptors measured with alpha-bungarotoxin (BTX). Strain differences in the development of tolerance to nicotine were also observed. Four mouse strains were tested and one of these strains (C3H) did not exhibit tolerance to nicotine. The binding of (3H)nicotine and (125I)BTX increased in the brains of all four mouse strains. These changes may relate to tolerance in some mouse strains, but since C3H mice did not exhibit tolerance even though brain nicotinic receptors changed following chronic treatment, other explanations for the role of receptor changes in tolerance to nicotine must be sought.
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PMID:Genetic influences on acute responses to nicotine and nicotine tolerance in the mouse. 317 52

Male and female long-sleep (LS) and short-sleep (SS) mice were pretreated with a subseizure-producing dose of nicotine (2.0 mg/kg) 7.5, 15 and 30 minutes prior to challenge with seizure-producing doses of this drug. Nicotine pretreated animals were less susceptible to nicotine-induced seizures than were saline pretreated animals. The latency to seizure following nicotine challenge was greater in nicotine pretreated animals than in saline controls. Nicotine pretreated LS mice show a greater decrease in nicotine-induced seizure susceptibility than do nicotine pretreated SS mice. This decrease in seizure susceptibility is consistent with induction of nicotinic receptor desensitization via nicotine pretreatment. It is hypothesized that LS and SS mice might differ in sensitivity to nicotine in part because they differ in baseline levels of desensitized versus functional nicotinic receptors.
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PMID:Decreased sensitivity to nicotine-induced seizures as a consequence of nicotine pretreatment in long-sleep and short-sleep mice. 335 71

Nicotine base was used in a conditioned taste aversion (CTA) paradigm to avert male Sprague-Dawley rats to saccharin solution (0.1%, w/v). Experiments investigated different dose routes of nicotine administration and duration of action as determinants in nicotine-induced CTA. In Experiment 1 nicotine was injected intraperitoneally (IP) at doses of 0.5, 1.0, or 3.0 mg/kg 30 min after drinking saccharin solution. Using a two-bottle choice test, no CTA was observed, although all nicotine animals showed obvious symptoms of malaise including seizures in the highest dose group. Experiment 2 showed dose-related CTA when nicotine (10.0, 30.0, or 50.0 mg/kg) was cutaneously applied 30 min following saccharin drinking. Experiment 2B showed that the aversions were due to associative rather than nonassociative factors such as sensitization or enhanced neophobia. In Experiment 3, the following group treatments were begun 30 min after saccharin drinking to distribute identical total nicotine doses over an extended period of time: One IP injection of 2.0 mg/kg nicotine (in a saline vehicle) and four injections of saline solution, three injections of 0.67 mg/kg nicotine and two injections of saline, five injections of 0.40 mg/kg nicotine, or five injections of saline. All injections were spaced 30 min apart. Compared with saline-injected controls, CTA occurred in the rats receiving either three or five injections of nicotine but the group receiving one injection did not differ from the control group. There was no difference in CTA between the groups receiving three or five injections.
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PMID:Conditioned saccharin aversions in rats as a result of cutaneous nicotine or intraperitoneal nicotine administered in divided doses. 343 15

Nicotine response and nicotinic receptor binding were characterized in long-sleep (LS) and short-sleep (SS) mice which have been selectively bred for differential "sleep-time" following ethanol administration. LS mice are more sensitive than SS mice to nicotine as measured by a battery of behavioral and physiological tests and as measured by sensitivity to nicotine-induced seizures. The greater sensitivity of the LS mice is not due to differences in binding of [3H]nicotine. Unlike inbred mouse strains which differ in sensitivity to nicotine-induced seizures, these selected mouse lines do not differ in levels of binding of [125I]alpha-bungarotoxin (BTX) in the hippocampus. Significant differences in BTX binding were found in the cerebellum and striatum. Although these two mouse lines do not differ in blood levels of nicotine following nicotine administration, they differ slightly in brain levels of nicotine indicating differential distribution of the drug. Since this distribution difference is much smaller than the observed behavioral differences, these mice probably differ in CNS sensitivity to nicotine; however, follow-up studies are necessary to test whether the differential response of these mice is due to subtle differences in distribution of nicotine to the brain.
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PMID:Nicotine response and nicotinic receptors in long-sleep and short-sleep mice. 343 39

A classical F2 and backcross genetic design was used to examine the relationship between sensitivity to nicotine-induced seizures and hippocampal nicotinic receptors. Nicotine was administered by i.v. infusion through cannulas implanted in the right jugular veins of mice from the C3H and DBA mouse strains and their derived F1, F2 and backcross (F1 X C3H and F1 X DBA) generations. Nicotine-induced seizure sensitivity was assessed by infusing nicotine at a 2.0 mg/kg/min concentration until the onset of a clonic seizure. After seizure testing, mice were sacrificed and the binding of alpha-bungarotoxin (BTX) was determined in three brain regions: cortex, midbrain and hippocampus. The pattern of results for the six generations for seizure sensitivity was similar to that observed for hippocampal BTX binding. Genetic analyses indicate that receptor concentrations in the hippocampus and seizure sensitivity are both influenced by a relatively simple genetic system which involves one or more genes acting in an additive fashion. In addition, the genetic correlation which is indicative of the extent to which two characters are influenced by the same genes, supports the relationship between nicotine-induced seizure sensitivity and hippocampal BTX binding. The results suggest that those animals which are sensitive to nicotine-induced seizures have a greater concentration of nicotinic receptors as determined by the binding of BTX than animals which are less sensitive to the convulsant effects of nicotine.
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PMID:Genetic analysis of nicotine-induced seizures and hippocampal nicotinic receptors in the mouse. 379 45


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