The present study was performed in order to test the effects of diphenylhydantoin (DPH) and two central nervous system (CNS) stimulants, intermittent light stimulation(ILS) and pentylenetetrazol (Metrazol) on body temperature (Tb) during cold exposure in the bat DHP delayed the onset of entry into hibernation in both the oriental discoloured bats and the little brown bats and formed long and prominent plateaus that were not found in the normal and the controls. The responses of body temperature to the ILS were sensitive and the body temperature fell dramatically in the big brown bats. Metrazol effects on body temperature were obvious but; seemed dose-dependent. The experimental results further support the hypothesis that hibernation is an epileptic fit as suggested by serveral researchers.
Animal ; Body Temperature/drug effects ; Body Temperature Regulation ; Chiroptera/physiology* ; Female ; Hibernation* ; Light ; Male ; Pentylenetetrazole/pharmacology ; Phenytoin/pharmacology

Animals ; Anticonvulsants ; pharmacology ; Drug Evaluation, Preclinical ; methods ; GABA-A Receptor Antagonists ; pharmacology ; Motor Activity ; drug effects ; Pentylenetetrazole ; pharmacology ; Valproic Acid ; pharmacology ; Zebrafish

OBJECTIVETo investigate the effects and the mechanisms of the first-generation histamine H(1)-antagonist diphenhydramine and the second-generation histamine H(1)- antagonist fexofenadine on seizure development of pentylenetetrazole (PTZ)-induced kindling in rats.

METHODSThe first-or second-generation histamine H(1)-antagonists and/or histidine were ip injected in rats every 48 h, followed by a subconvulsive dose of PTZ (35 mg/kg). Then the behavioral changes were observed for 30 min after every injection of PTZ. The histamine content of brain was measured spectrofluorometrically.

RESULTCompared with the control group, diphenhydramine (5 mg/kg) significantly augmented the severity of seizure development of PTZ-induced kindling, whereas fexofenadine (5 mg/kg) had no marked influence. The effects of diphenhydramine were antagonized by histidine, the precursor of histamine.

CONCLUSIONSeizure development of PTZ-induced kindling is promoted by the first-but not the second generation histamine H(1)-antagonists via the blockade of brain histamine H(1)-receptor.

Animals ; Histamine ; physiology ; Histamine H1 Antagonists ; pharmacology ; Histamine H1 Antagonists, Non-Sedating ; pharmacology ; Histidine ; pharmacology ; Kindling, Neurologic ; drug effects ; Male ; Pentylenetetrazole ; Rats ; Rats, Sprague-Dawley ; Seizures ; chemically induced

OBJECTIVETo investigate the effects of antisense glutamic acid decarboxylase (GAD(67)) oligodeoxynucleo-tide (ODN) on behavior, seizure threshold and EEG of hippocampus in the epileptic rats induced by pentylenetetrazol (PTZ).

METHODSA model of chronic epilepsy in rats was established by PTZ. The inhibition of GAD(67) mRNA expression in hippocampus was selectively induced by antisense oligodeoxynucleotide of GAD(67). The effect of antisense GAD(67) ODN on behavior, seizure threshold and EEG recording of kindled rats was examined.

RESULTSAntisense GAD(67) ODN could inhibit the expression of GAD(67) mRNA and the concentration of GABA. It also could significantly shorten the latencies of seizure and increase the level of seizure and the frequency of epileptiform discharges.

CONCLUSIONThe gene of GAD(67) may be an anti-seizure gene, which might inhibit epileptiform discharge. The treatment of epilepsy by GAD(67) gene will have a bright future.

Animals ; Electroencephalography ; Epilepsy ; chemically induced ; physiopathology ; Glutamate Decarboxylase ; genetics ; pharmacology ; Hippocampus ; physiopathology ; Isoenzymes ; genetics ; pharmacology ; Kindling, Neurologic ; Male ; Oligonucleotides, Antisense ; pharmacology ; Pentylenetetrazole ; Rats ; gamma-Aminobutyric Acid ; analysis

The influence of 3α-androstanediol (3α-diol) on twitch and electroencephalogram (EEG) of the epileptic rats induced by pentylenetetrazole (PTZ) has been observed in this experiment in order to comprehensively explore the role of 3α-diol on epileptic attack from the aspects of behavior and EEG. Thirty-two male Sprague-Dawley rats were evenly and randomly divided into 4 groups: the normal and supplied with oil epileptic (N+oil+PTZ) group, the normal and supplied with 3α-diol epileptic (N+3α-diol+PTZ) group, the gonadectomized and supplied with oil epileptic (GDX+oil+PTZ) group and the gonadectomized and supplied with 3α-diol epileptic (GDX+3α-diol+PTZ) group. The changes of the behavior and EEG of epileptic rats in every group were recorded and analyzed. The results of behavior observation showed that the latency to clonic seizure and tonic-clonic seizure was shortened and the number of tonic-clonic seizure was increased significantly in the GDX+oil+PTZ group in comparison with N+oil+PTZ group (P < 0.05); comparing GDX+3α-diol+PTZ group with GDX+oil+PTZ group, or N+3α-diol+PTZ group with N+oil+PTZ group, we found that the latency to clonic seizure and tonic-clonic seizure became prolonged significantly, and the number of clonic seizure and tonic-clonic seizure was decreased significantly (P < 0.05). The results of EEG showed that the latency to epileptic waves was cut and the number of epileptic waves was augmented significantly in the GDX+oil+PTZ group in comparison with N+oil+PTZ group (P < 0.05); comparing GDX+3α-diol+PTZ group with GDX+oil+PTZ group, or N+3α-diol+PTZ group with N+oil+PTZ group, we found that the latency to epileptic waves became lengthened significantly, the number of epileptic waves was reduced significantly and the percentage of change of TP (total power of spectrum) was lessened significantly (P < 0.05). These results indicate that 3α-diol has an antiepileptic activity in the gonadectomized and normal epileptic rats.
Androstane-3,17-diol ; analogs & derivatives ; pharmacology ; Animals ; Anticonvulsants ; pharmacology ; Electroencephalography ; Epilepsy ; chemically induced ; drug therapy ; Male ; Pentylenetetrazole ; adverse effects ; Rats ; Rats, Sprague-Dawley ; Seizures ; chemically induced ; drug therapy

Action Potentials ; drug effects ; Animals ; CA1 Region, Hippocampal ; cytology ; Drug Antagonism ; Male ; Neurons ; drug effects ; Pentylenetetrazole ; pharmacology ; Propofol ; pharmacology ; Rats ; Rats, Wistar ; Synaptic Transmission ; drug effects

OBJECTIVETo investigate the mechanisms of histamine on chronic epilepsy induced by pentylenetetrazole (PTZ).

METHODSTo induce chemical kindling, a subconvulsive dose (35mg/kg) of PTZ was ip injected every 48 h in rats. Behavior changes were observed for 30 min after every injection of PTZ.

RESULTIp injection of histidine or icv injection of clobenpropit inhibited the development of kindling induced by PTZ, presenting prolonged latency for myoclonic jerks and clonic generalized seizures and depressed seizure stages in a dose-dependent manner. H(3)receptor agonist, immepip, and histidine decarboxylase, alpha-fluoromethylhistidine reversed the ameliorating effect of clobenpropit on seizure development in a dose-dependent manner.

CONCLUSIONBrain histamine plays an important role in protection against myoclonic jerks and clonic generalized clonic seizures and its action may be via H(3)receptor.

Animals ; Brain ; physiology ; Chronic Disease ; Dose-Response Relationship, Drug ; Epilepsy ; chemically induced ; Histamine ; physiology ; Histidine ; pharmacology ; Imidazoles ; pharmacology ; Male ; Pentylenetetrazole ; pharmacology ; Piperidines ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Thiourea ; analogs & derivatives ; pharmacology

OBJECTIVETo investigate the effect of alahistidine on brain histamine content and seizure development.

METHODSThe kindling seizure was induced by ip injection with subconvulsant dose of pentylenetetrazole every 48 h. Monoamines and their metabolites were measured using a HPLC system and fluorometric assay.

RESULTChronic low histamine feeding markedly decreased histamine content in cortex and hypothalamus, and promoted seizure development induced by pentylenetetrazole. However, alahistidine feed reversed the decreased histamine content and slowed seizure development caused by low histamine feed. Both low histamine and alahistidine feed had no effect on norepinephrine, dopamine and its metabolites.

CONCLUSIONAlahistidine may affect histaminergic system and seizure development.

Animals ; Brain Chemistry ; drug effects ; Carnosine ; analogs & derivatives ; pharmacology ; Histamine ; analysis ; Male ; Pentylenetetrazole ; Rats ; Rats, Sprague-Dawley ; Receptors, Histamine H1 ; physiology ; Seizures ; chemically induced

OBJECTIVETo investigate the effect of saikosaponin alpha (SSalpha) on experimental epilepsy in rats.

METHODSAcute epileptic seizure was induced by pentylenetetrazole (PTZ) in rats, and the seizure incubation period and the number of rats with tetanic convulsion were recorded to study the antiepileptic effect of SSalpha.

RESULTSAfter treatment with SSalpha, the incubation period of PTZ-induced seizure was significantly prolonged (P<0.01), and the rate of tetanic convulsion was significantly reduced (P<0.05).

CONCLUSIONSSalpha can inhibit epileptic seizure induced by PTZ.

Animals ; Anti-Inflammatory Agents, Non-Steroidal ; pharmacology ; Anticonvulsants ; pharmacology ; Epilepsy ; chemically induced ; prevention & control ; Female ; Male ; Oleanolic Acid ; analogs & derivatives ; pharmacology ; Pentylenetetrazole ; Rats ; Rats, Sprague-Dawley ; Saponins ; pharmacology ; Time Factors

BACKGROUNDHistamine H(3) receptor antagonists have been considered as potential drugs to treat central nervous system diseases. However, whether these drugs can inhibit epileptogenesis remains unclear. This study aimed to investigate the effects of thioperamide, a selective and potent histamine H(3) receptor antagonist, on the seizure development and memory impairment induced by pentylenetetrazole (PTZ)-kindling epilepsy in rats.

METHODSChemical kindling was elicited by repeated intraperitoneal (ip) injections of a subconvulsant dose of PTZ (35 mg/kg) once every 48 hours for 12 times, and seizure activity of kindling was recorded for 30 minutes. Control rats were ip injected with saline instead of PTZ. Morris water maze was used to evaluate the spatial memory. Phosphorylated cyclic adenosine monophosphate response element binding protein (p-CREB) was tested by Western blotting in hippocampus.

RESULTSIntracerebroventricular (icv) injections with thioperamide (10 µg, 20 µg) 30 minutes before every PTZ injections, significantly prolonged the onset of PTZ-kindling and inhibited the seizure stages. PTZ-kindling seizures led to the impairment of spatial memory in rats, and thioperamide ameliorated the impairment of spatial learning and memory. Compared to non-kindling rats, there was a significant decrease in p-CREB level in hippocampus of the PTZ-kindling rats, which was reversed by thioperamide.

CONCLUSIONSThioperamide plays a protective role in seizure development and cognitive impairment of PTZ-induced kindling in rats. The protection of thioperamide in cognitive impairment is possibly associated with the enhancement of CREB-dependent transcription.

Animals ; Anticonvulsants ; pharmacology ; Cyclic AMP Response Element-Binding Protein ; metabolism ; Histamine H3 Antagonists ; pharmacology ; Kindling, Neurologic ; drug effects ; Male ; Memory Disorders ; prevention & control ; Neuroprotective Agents ; pharmacology ; Pentylenetetrazole ; Piperidines ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Seizures ; prevention & control ; Synaptic Transmission