Changes of visual evoked potential induced by lateral geniculate nucleus kindling in rats.

PURPOSE: The present study was undertaken to investigate the changes of visual evoked potential (VEP) induced by lateral geniculate nucleus (LGN) kindling in comparison with those induced by amygdala (AMG) and hippocampus (HPC) kindling in rats. METHODS: Under pentobarbital anesthesia, the rats were fixed to a stereotaxic apparatus, and stainless steel electrodes were implanted into the LGN, AMG, HPC and the occipital cortex (OCOR). Bipolar stimulation was applied to the LGN, AMG or HPC every day until generalized seizure was obtained. VEP was recorded from the OCOR before the first day of electric stimulation (pre-kindled) and after the development of kindling (post-kindled). RESULTS: After the development of LGN kindling, the amplitudes of early VEP components (P(1)-N(1) and N(1)-P(2)) were significantly augmented in comparison with those of pre-kindled rats. In addition, the duration of the photically evoked after-discharge burst (duration of VEP) was significantly prolonged by LGN kindling. On the other hand, in AMG and HPC kindling, no significant changes were observed in VEP between pre-kindled and post-kindled rats. CONCLUSIONS: The changes of VEP observed in patients with photosensitive epilepsy are also demonstrated in animal study using LGN kindling.

Effects of certain antiepileptics on behavioral and electromyographic seizure patterns induced by maximal electroshock in mice.

The changes of electromyographic activity (EMG seizure) induced by maximal electroshock were studied in comparison with those of behavioral seizures in mice. In addition, the effects of certain antiepileptics on behavioral seizures and EMG seizure induced by maximal electroshock were also studied. High amplitude with high frequency EMG seizure was observed in parallel with the appearance of tonic extensor (TE) seizure and an intimate relationship was observed between the two parameters. On the other hand, to investigate the intensity of TE seizure, the product of the amplitude and the duration in EMG seizure was calculated, and the effects of antiepileptics on the magnitude of EMG seizure were investigated. As a result, a significant difference was observed at the doses of antiepileptics that showed no significant effects on the durations of TE and EMG seizures; that is, phenytoin, phenobarbital, topiramate, and carbamazepine showed significant effects on the magnitude of EMG seizure at doses of 5, 2, 10, and 5 mg/kg, respectively. From these findings, it may be concluded that this index, that is, the magnitude of EMG seizure induced by maximal electroshock, is a more reliable and highly sensitive method for the assessment of the potential activity of antiepileptics.

Influences of histamine H1 receptor antagonists on maximal electroshock seizure in infant rats.

The influences of histamine H1 receptor antagonists on maximal electroshock seizure were studied using infant rats. In this study, electroconvulsion was induced by stimulating rats using ear-clip electrodes, and the durations of electroencephalogram (EEG) seizure, tonic extensor (TE) seizure and clonic (CL) seizure induced by maximal electroshock were measured. Diphenhydramine, chlorpheniramine, cyproheptadine and ketotifen caused a dose-dependent and significant prolongation of both EEG seizure and TE seizure induced by maximal electroshock. On the other hand, epinastine and fexofenadine caused no such effects, even at a dose of 50 mg/kg. All drugs used in this study showed no significant effect on CL seizure induced by maximal electroshock. From these findings, it is suggested that epinastine and fexofenadine may cause no harmful influence on epilepsy, even when used in a little child.

Epileptiformic activity induced by antidepressants in amygdala-kindled rats.

The present study was undertaken to investigate the spontaneous epileptiformic activity induced by antidepressants using amygdala-kindled rats. The intraperitoneal injection of imipramine and amitriptyline resulted in potent behavioral and electroencephalogram (EEG)-detected seizures in amygdala-kindled rats compared with those seen in sham rats (non-kindled rats). Almost the same findings were observed with clomipramine and maprotiline. On the other hand, paroxetine caused no or little behavioral or EEG seizures in either amygdala-kindled or sham rats, even at a dose of 50 mg/kg. In conclusion, our results indicate that epileptiformic activity induced by kindling increases the susceptibility to cyclic antidepressant-induced seizures.

Interactive effect of histamine and prostaglandin D2 on nasal allergic symptoms in rats.

This study was undertaken to investigate the interactive effect of histamine and prostaglandin D(2) in nasal allergic symptoms in rats. The intranasal application of histamine at doses lower than 10 mumol/site caused no sneezing or nasal rubbing. In addition, prostaglandin D(2) also showed no significant increase in these responses, even at a dose of 10 nmol/site. On the other hand, the simultaneous instillation of histamine and prostaglandin D(2) resulted in a 1000 times more potent effect in inducing nasal symptoms than the administration of histamine alone. Thus, prostaglandin D(2) enhanced the actions of histamine in inducing sneezing and nasal rubbing in a dose-dependent manner, and significant effects were observed at doses higher than 1 nmol/site. The responses induced by the simultaneous application of histamine and prostaglandin D(2) were inhibited by chlorpheniramine, cyproheptadine, BW A868C and ramatroban. Chlorpheniramine and cyproheptadine showed the dose-related inhibition of nasal symptoms induced by the combined administration of histamine (10 nmol) and prostaglandin D(2) (10 nmol), but the effect of cyproheptadine was relatively weak compared with chlorpheniramine. Moreover, BW A868C and ramatroban also showed the inhibition of nasal symptoms induced by the simultaneous administration of histamine and prostaglandin D(2) in a dose-dependent manner. BW A868C was more potent in inhibiting the nasal symptoms than ramatroban. These results clearly indicate that prostaglandin D(2) showed a synergistic effect on sneezing and nasal rubbing induced by histamine in rats, and its effect occurred through both prostaglandin D(2) and CRTH2 (chemoattractant receptor-homologous molecule expressed on TH2 cells) receptors.

Epileptogenic activity of methicillin-resistant Staphylococcus aureus (MRSA) antibiotics in rats.

The present study was undertaken to clarify the epileptogenic activity induced by intracerebroventricular injection (i.c.v.) of antibiotics effective in methicillin-resistant Staphylococcus aureus (MRSA) in chronically electrode implanted rats. Teicoplanin (10-100 microg, i.c.v.) caused dose-related electroencephalographic (EEG) seizure characterized by an uninterrupted high voltage and wave complex. At the same time, the rats showed forelimb clonus, head nodding, jumping and severe convulsion. At a high dose (100 microg, i.c.v.), the drug caused a severe twisting immediately after the intracerebroventricular injection (i.c.v.) followed by jumping and violent convulsion with a continuous rhythmic spike and wave complex in EEG. On the other hand, vancomycin (30-1000 microg, i.c.v.) caused no or almost no epileptogenic activity in terms of behavior and in EEG. However, at a high dose (1000 microg, i.c.v.), the drug caused an occasional spike from the hippocampus without showing any behavioral changes in the rats. Fosfomycin (30-1000 microg, i.c.v.), cefazolin (10-100 microg, i.c.v.) and penicillin G (30-300 microg, i.c.v.), used as reference drugs, caused dose-dependent epileptogenic activity in both EEG. From these findings, it was found that teicoplanin caused a potent epileptogenic activity, different to vancomycin. Therefore, it can be concluded that vancomycin may be safety on epileptogenic activity used for the clinical purpose of infections caused by MRSA.

Mechanism of imipramine-induced seizures in amygdala-kindled rats.

The present study was undertaken to get insight in the possible mechanisms of imipramine-induced seizures in amygdala-kindled rats. The intraperitoneal (i.p.) injection of imipramine produced potent behavioral and electroencephalogram (EEG) seizures in amygdala-kindled rats. Histidine (1500 mg/kg, i.p.) and histamine (10 and 20 microg, i.c.v.) significantly attenuated the seizures induced by imipramine (50 mg/kg, i.p.) in kindled rats. In addition, the inhibition of imipramine-induced seizures by histamine (20 microg, i.c.v.) was antagonized by an H1 antagonist, pyrilamine. An H3 antagonist, thioperamide (50 microg, i.c.v.), also significantly attenuated the imipramine-induced seizures in kindled rats. The i.p. injection of alpha-methyl-p-tyrosine at a dose of 250 mg/kg significantly diminished the seizures induced by imipramine. However, p-chlorophenylalanine and physostigmine did not affect the imipramine-induced seizures to any extent. These data give strong hints that the H1 receptor antagonistic properties and the brain noradrenaline activating effects of imipramine are centrally involved in imipramine-induced seizures, and central serotonergic and cholinergic neurotransmissions are not involved in the seizures induced by imipramine in amygdala-kindled rats.

Effects of some antiepileptics on septal-kindled seizures in rats.

PURPOSE: The present study was performed to understand the characteristics of septal kindling in rats, especially the efficacies of antiepileptic drugs in comparison with amygdala kindling. METHODS: Under pentobarbital anesthesia, rats were fixed to a stereotaxic apparatus, and electrodes were implanted into the right frontal cortex, the hippocampus, the lateral septal and the amygdala. Electrodes were connected to a miniature receptacle, which was embedded in the skull with dental cement. Bipolar stimulation was applied to the lateral septal or the amygdala every day until a generalized seizure was obtained. Carbamazepine (CBZ), zonisamide (ZNS) and clobazam (CLB) were orally administered to fully kindled rats. RESULT: A considerable number of stimulations was required to establish septal-kindled seizures. In addition, wet dog shakes were observed during the septal kindling procedure, different from amygdala kindling. The oral administration of CBZ, ZNS and CLB caused a dose-dependent inhibition both of seizure stage and after-discharge (AD) duration of septal-kindled seizures. CBZ and ZNS caused a more potent inhibition of septal-kindled seizures than amygdala kindled seizures, whereas CLB inhibited both septal and amygdala kindled seizures to almost the same extent. CONCLUSION: Septal kindling was confirmed to possess some characteristics, which were evidently different from that of amygdala kindling. In addition, it was demonstrated that septal kindling was also available as a model for the evaluation of antiepileptic drugs.