Scopolamine-induced Convulsions Research Articles

P.1.g.040 - Scopolamine-induced convulsions in fasted mice after food intake: determination of M1 and M2 muscarinic receptor expressions in brain regions

P.1.g.040 - Scopolamine-induced convulsions in fasted mice after food intake: determination of M1 and M2 muscarinic receptor expressions in brain regions

P.1.g.083 - Scopolamine-induced convulsions in fasted mice after food intake: the evaluation of the contribution of M1 and M2 muscarinic receptor subtypes

P.1.g.083 - Scopolamine-induced convulsions in fasted mice after food intake: the evaluation of the contribution of M1 and M2 muscarinic receptor subtypes

Scopolamine-induced convulsions in fasted animals after food intake: Sensitivity of C57BL/6J mice and Sprague-Dawley rats

Food intake triggers convulsions in fasted BALB/c mice and Wistar albino rats treated with antimuscarinic drugs, scopolamine or atropine. Inbred strain studies have yielded considerable information regarding genetic influences on seizure susceptibility and factors contribute to epileptogenesis in rodents. This study, therefore, investigated sensitivity to antimuscarinic-induced seizures in C57BL/6J mice and Sprague-Dawley rats. Food deprivation for 48h in mice and 52h in rats did not produce strain differences in body weight loss. Fasted animals treated i.p. with 3mg/kg scopolamine developed convulsions after food intake. The incidence of convulsions was indifferent in comparison to BALB/c mice and Wistar albino rats. Number of animals developing stage 5 was more and onset of convulsions was longer in C57BL/6J mice than in BALB/c mice. Strain-related differences in sensitivity to seizures in C57BL/6J mice may need further evaluation for investigating genetic influences on scopolamine-induced seizures.

Scopolamine-induced convulsions in fasted mice after food intake: Evaluation of the sedative effect in the suppression of convulsions

Food intake triggers convulsions in fasted mice and rats treated with antimuscarinic drugs, scopolamine or atropine. Most of the drugs produced anticonvulsant efficacy in these convulsions have sedative effects. Thus, the present study was performed to evaluate the contribution of sedation in the suppression of convulsions by using sedative drugs chlorpromazine, morphine, amitriptyline and diphenhydramine. Mice fasted for 24h and treated with 3mg/kg scopolamine developed convulsions soon after refeeding. Treatment of chlorpromazine and morphine during food deprivation did not provide a preventive effect in the development of convulsions observed after food intake in fasted animals. Pretreatment of amitriptyline, but not diphenhydramine, before scopolamine treatment suppressed the incidence of convulsions. Present results could not clearly demonstrate the role played by sedative effect in suppression of convulsions in fasted animals.

The role of solid food intake in antimuscarinic-induced convulsions in fasted mice

Animals treated with scopolamine after fasting develop convulsions after they are allowed to eat ad libitum. This study was aimed at investigating the effect on these convulsions of liquid food intake, feeding by gavage, and placebo. Fasted mice treated with saline or scopolamine were allowed to eat solid food, slurry food or liquid food ad libitum, given placebo, or given liquid food by gavage. After 30 min, all animals were allowed to eat food pellets and observed for 30 min for the incidence and onset of convulsions. Scopolamine treatment caused convulsions only in the animals given solid food in the first 30 min; no convulsions were observed in the animals given slurry food, liquid food ad libitum, gavage, or placebo. When the animals that did not develop convulsions during the experiment were allowed to eat solid food, convulsions occurred. These findings indicate that complex mechanisms trigger scopolamine-induced convulsions in fasted animals eating solid food.

The evaluation of antimuscarinic-induced convulsions in fasted rats after food intake

The present study was performed to evaluate convulsions after food intake in fasted rats pretreated with scopolamine or atropine and to determine whether these convulsions respond to drugs found effective in fasted mice. Scopolamine (2.4 mg/kg) and atropine (2.4 mg/kg) were given intraperitoneally (i.p.) to rats fasted for 52 h. Both drugs induced convulsions after animals were allowed to eat ad lib. Another group of fasted rats pretreated with saline, MK-801 (0.1 mg/kg), clonidine (0.1 mg/kg), chlorpromazine (2 and 4 mg/kg), valproate (200 mg/kg), diazepam (1.5 and 2 mg/kg) or gabapentin (50 mg/kg) were treated i.p. with saline or scopolamine (2.4 mg/kg) and were allowed to eat ad lib. Clonidine, MK-801, chlorpromazine (4 mg/kg) and diazepam (2 mg/kg) reduced the incidence of scopolamine-induced convulsions in fasted rats. Gabapentin could only prolong the onset of convulsions. Neither treatment was effective against myoclonus of hindlimbs. Present results showed that fasted rats also develop antimuscarinic-induced convulsions which do not completely respond to treatments found effective in convulsions of fasted mice.

Electroencephalographic characterization of scopolamine-induced convulsions in fasted mice after food intake

The present study was conducted to evaluate scopolamine-induced convulsions in fasted mice after food intake effects on the cortical electroencephalogram (EEG). Continuous EEG recordings were taken with Neuroscan for 10 min in freely moving mice with six chronic cortical electrode implants. Animals were weighed and deprived of food for 48 h. EEG recordings were taken at the 24th and 48th hour after their food deprivations. Later, all animals were treated with saline or scopolamine of 3mg/kg i.p. and EEG recordings were repeated for 10 min. Twenty minutes later, they were given food pellets and were allowed to eat ad libitum. All animals were observed for 60 min to determine the incidence and onset of convulsions and EEG recordings were taken simultaneously. The present results demonstrate that food deprivation causes differences in EEG in the elapsed time. The changes in EEG induced after food deprivation become different with scopolamine administration. In scopolamine treatment group, eating caused a series of high-voltage polyspikes and synchronized spikes with a predominant frequency in the 1-3 Hz range and fast activity that represents a typical epileptiform manifestation. It was concluded that the EEG properties and the behavioral patterns of these convulsions are in accordance with each other.

Scopolamine-induced convulsions in fasted mice after food intake: effects of glucose intake, antimuscarinic activity and anticonvulsant drugs

The present study was performed to further evaluate the contribution of antimuscarinic activity and hypoglycaemia to the development of scopolamine-induced convulsions in fasted mice after food intake. The effects of anticonvulsant drugs on convulsions were also evaluated. Antimuscarinic drugs atropine (3 mg/kg) and biperiden (10 mg/kg) were given intraperitoneally (i.p) to animals fasted for 48 h. Like scopolamine, both drugs induced convulsions after animals were allowed to eat ad libitum. Another group of animals was given glucose (5%) in drinking water during fasting. These animals, although they had normoglycaemic blood levels after fasting, also developed convulsions after treated with scopolamine i.p. (3 mg/kg), atropine (3 mg/kg) or biperiden (10 mg/kg) and allowed to eat ad libitum. Among the drugs studied, only valproate (340 mg/kg), gabapentin (50 mg/kg) and diazepam (2.5 and 5 mg/kg) markedly reduced the incidence of scopolamine-induced convulsions. The present results indicate that antimuscarinic activity, but not hypoglycaemia, underlies these convulsions which do not respond to most of the conventional anticonvulsant drugs.

Scopolamine-induced convulsions in fasted mice after food intake: determination of blood glucose levels, [ 3H]glutamate binding kinetics and antidopaminergic drug effects

The present study was performed to evaluate the role(s) of hypoglycemia, changes in [ 3H]glutamate binding kinetics and dopaminergic activity in the occurrence of scopolamine-induced convulsions in fasted mice after food intake. Plasma glucose levels and density ( B max) and affinity ( K d) of [ 3H]glutamate binding sites in whole brain synaptic membranes were determined in animals fed ad lib or fasted for 48 h and treated intraperitoneally (i.p.) with 3 mg/kg scopolamine or saline and allowed to eat for 5 min. Fasting for 48 h decreased plasma glucose levels. After refeeding, plasma glucose concentrations increased in saline treated animals, but remained unchanged in scopolamine treated animals which consumed less food. Fasting for 48 h also produced significant changes in the kinetics of [ 3H]glutamate binding. The B max and K d of the binding sites decreased in fasted animals. These changes were partially antagonized by scopolamine treatment and food intake. For the evaluation of the contribution of dopaminergic activity, another group of mice fasted for 48 h and pretreated (i.p.) with saline or dopamine antagonists, 2 mg/kg chlorpromazine or 2 or 4 mg/kg haloperidol, were treated 10 min later with either saline or 3 mg/kg scopolamine. Then 20 min later, they were allowed to eat ad lib and were observed for 30 min for the incidence and onset of clonic convulsions. Pretreatment of both 2 mg/kg chlorpromazine and 4 mg/kg haloperidol markedly suppressed the convulsions. These results indicate that the decrease in the [ 3H]glutamate binding induced by fasting, its antagonism by scopolamine treatment and food intake, and the dopaminergic hyperactivity may be possible factors contributing to the occurrence of convulsions.

Scopolamine-induced convulsions in food given fasted mice: Long-term evaluation of the nociceptive response

Scopolamine-induced convulsions in food given fasted mice: Long-term evaluation of the nociceptive response

Scopolamine-induced convulsions in food given fasted mice: effects of clonidine and tizanidine

We recently reported that scopolamine pretreated mice fasted for 48 h developed clonic convulsions soon after they were allowed to eat ad libidum. Pretreatment with MK-801, the non-competitive NMDA antagonist, decreased the incidence of these convulsions. We suggested that a possible scopolamine-induced glutamatergic hyperactivity could account for these convulsions. Using α 2-agonists, clonidine, which has been shown to inhibit glutamate release, and tizanidine, the present study was performed to find some additional data for the role of glutamate in the underlying mechanism of scopolamine-induced convulsions in food given fasted mice. Animals fasted for 48 h and pretreated (i.p.) with saline, clonidine (0.05, 0.10, 1 mg/kg) or tizanidine (0.10, 0.15, 0.30, 0.45 mg/kg) were treated (i.p.) with either saline or scopolamine (3 mg/kg). Then 20 min later, they were allowed to eat ad libidum and were observed for 30 min for the incidence and onset of clonic convulsions. All doses of clonidine pretreatment completely suppressed (0%) scopolamine-induced clonic convulsions (75%). On the other hand, only 0.15 mg/kg tizanidine pretreatment significantly decreased (15%) the incidence of convulsions; however as well as 0.15 mg/kg, both 0.30 and 0.45 mg/kg tizanidine pretreatments significantly increased latency to the onset of convulsions.

Scopolamine-induced convulsions in food given fasted mice: effects of physostigmine and MK-801.

We recently reported that scopolamine pretreated mice fasted for 48 h developed clonic convulsions soon after they were allowed to eat a small amount of food for 30 s. The present experiments were performed to determine whether animals also develop convulsions when they were allowed to eat ad libitum and to find some evidence for the contribution of the cholinergic and/or glutamatergic systems in the underlying mechanism(s) of convulsions. Animals fasted for 48 h were treated with 3 mg/kg scopolamine or saline. Twenty minutes later, they were allowed to eat either ad libitum or a small portion of food for 30 s. Scopolamine pretreated animals after starting to eat ad libitum or a small amount in a restricted time developed convulsions in a few minutes, the incidence being 76 and 54%, respectively. Pretreatment of 0.17 mg/kg MK-801, the noncompetitive NMDA antagonist, decreased the incidence of scopolamine-induced convulsions (22%) without affecting latency to the onset of seizures. Pretreatment of 0.1 mg/kg physostigmine, the cholinesterase inhibitor, changed neither the incidence (90%) nor latency to the onset of scopolamine-induced convulsions.