Summary Purpose:  The present study was undertaken to clarify the effects of (RS)‐1‐aminoindan‐1,5‐dicarboxylic acid (AIDA), a metabotropic glutamate receptor (mGluR) 1 antagonist, (2R,4R)‐4‐aminopyrrolidine‐2,4‐dicarboxylate ((2R,4R)‐APDC), a mGluR2/3 agonist, and L‐(+)‐2‐amino‐4‐phosphonobutyric acid (L‐AP4), a mGluR4/8 agonist, on pentetrazol‐induced kindled seizures. Methods:  Mice were anesthetized with pentobarbital; the electrodes and guide cannula were chronically implanted into the cortex and lateral ventricle. To induce kindling, pentetrazol at a dose of 40 mg/kg was injected once every 48 h. Behavioral and electroencephalographic seizures were monitored for 20 min following pentetrazol administration. Fully kindled mice were used for pharmacologic studies. Results:  Intracerebroventricular injection of AIDA and L‐AP4 showed significant inhibitory effects on pentetrazol‐induced kindled seizures. In addition, simultaneous use of AIDA and (2R,4R)‐APDC or L‐AP4 caused more potent inhibition of seizure activities. The inhibitory effect of AIDA on pentetrazol‐induced kindled seizures was antagonized by (RS)‐3,5‐dihydroxyphenylglycine ((RS)‐3,5‐DHPG), a group I mGluR agonist; (2S)‐a‐ethylglutamic acid (EGLU), a group II mGluR antagonist; and (RS)‐α‐methyl‐4‐phosphonophenylglycine (MPPG), a group III mGluR antagonist. On the other hand, the inhibitory effect of L‐AP4 was antagonized only by MPPG. Discussion:  It is proposed that mGluR1 antagonists and mGluR4/8 agonists show anticonvulsive effects on pentetrazol‐induced kindled seizures. Furthermore, it is also proposed that the simultaneous use of an mGluR1 antagonist and an mGluR2/3 or mGluR4/8 agonist is a potential novel therapeutic strategy in epileptic disorders.

Electrogastrography (EGG) is a non-invasive diagnostic motility for recording gastric myoelectrical activity. Gastric myoelectrical activity was first recorded in 1922. Advances in recording equipment enabled widespread use of cutaneous EGG after 1985. Later, introduction of multichannel EGG (M-EGG) enabled measurement of electrical activity transmission. At present, M-EGG findings are used as objective indicators of gastric motility disorders caused by various diseases. EGG measures two categories of gastric electrical activity: electrical response activity, or spike potentials; and electrical control activity, or slow waves. The appearance of abnormal rhythmic electrical activity is indicative of abnormalities in gastric motility. The normal frequency range of gastric electrical activity (normogastria) is around 3 cycles per min. Multiple EGG parameters assist in the assessment of gastric myoelectrical activity, and significant correlations between EGG and other gastric motility tests have been demonstrated in many studies. In Japan, however, EGG remains in the exploratory stage, and its clinical use is limited. There are large variations in procedures and systems used in previous studies, thus there is a need for standardization of EGG procedures and technical terminology. Here, we outline the current status of EGG and report the M-EGG procedures used in our department in addition to our M-EGG findings.The abstract of this manuscript was presented during an educational seminar titled "Current status of gastrointestinal motility tests and keys for immediate implementation" at the 54th Annual Meeting of the Japan Society of Smooth Muscle Research

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SUMMARYPurpose: The present study was undertaken to clarify the behavioral and electroencephalographic characteristics of olfactory bulb (OB) kindling in rats, in comparison with those of amygdala (AMG) kindling. In addition, the usefulness of OB kindling as a model to evaluate antiepileptics was studied. Methods: Bipolar electrical stimulation was applied to the OB or AMG every day until generalized seizure was achieved. Antiepileptics (carbamazepine, sodium valproate, zonisamide, clobazam, and topiramate), which are used for complex partial epilepsy or secondary generalized epilepsy in clinical practice, were orally administrated to kindled rats. Results: The afterdischarge (AD) threshold of OB kindling is not different from that of AMG kindling. OB-kindled rats showed more rapid development of the seizure stage and AD duration than AMGkindled rats; however, fully kindled AD duration did not differ between groups. In AMG kindled rats, AD on day 1 was localized only at the stimulation site, whereas in OB-kindled rats, AD on day 1 was observed at not only the stimulation site (OB) but also in the frontal cortex, hippocampus, and AMG. All five antiepileptics significantly inhibited both the seizure stage and AD duration in OB-kindled rats. In addition, carbamazepine, zonisamide, and topiramate were more effective in suppressing OB-kindled seizures. Zonisamide was not effective at any dose tested in AMG-kindled rats. Discussion: OB kindling can be used as a new valuable model to evaluate antiepileptic drugs, with the advantage of its rapid development and the efficacy of antiepileptics.

The present study was undertaken to clarify the effect of group I metabotropic glutamate receptor (mGluR) antagonist, (RS)-1-aminoindan-1,5-dicarboxylic acid (AIDA) on pentetrazol-induced kindled seizures. The mechanism of the anticonvulsant effect of AIDA was also studied. Mice were anesthetized with pentobarbital; the electrodes and guide cannula were chronically implanted into the cortex and lateral ventricle. In order to induce kindling, pentetrazol at a dose of 40 mg/kg was injected intraperitoneally once every 48 h. Behavioral and electroencephalographic (EEG) seizures were observed for 20 min following pentetrazol administration. Intracerebroventricular (i.c.v.) injection of AIDA (1000 nmol/site) resulted in a significant inhibitory effect on pentetrazol-induced kindled seizures, and this effect was antagonized by a group I mGluR agonist, (RS)-3,5-dihydroxyphenylglycine ((RS)-3,5-DHPG). The effect of AIDA (200 nmol/site) on pentetrazol-induced kindled seizures was augmented by the simultaneous use of g g-aminobutyric acid (GABA) mimetic drugs, such as NNC-711 and diazepam. Moreover, the effect of AIDA (1000 nmol/site) on pentetrazol-induced kindled seizures was antagonized by a GABA A receptor antagonist, bicuculline and a GABA C receptor antagonist, (1,2,5,6-tetrahydropyridin-4-yl) methylphosphinic acid (TPMPA). It can be concluded that AIDA had an anticonvulsant effect on pentetrazol-induced kindled seizures, which was partially mediated by the GABAergic mechanism through GABA A and GABA C receptors.