Hidehiro Hasegawa
Kanazawa University
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Publication
Featured researches published by Hidehiro Hasegawa.
Neuroscience Letters | 1992
Yuji Wada; Mitsuhiko Nakamura; Hidehiro Hasegawa; Nariyoshi Yamaguchi
This study assessed the effects of a serotonin (5-HT)1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), a 5-HT2 agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and a 5-HT2 antagonist ketanserin on fully kindled seizures from the hippocampus. 8-OH-DPAT produced a marked suppression in hippocampal kindled seizures, while producing behavioral signs similar to those seen in the 5-HT syndrome. Although DOI and ketanserin did not affect kindled focal epileptic activity, DOI shortened and ketanserin prolonged the latency to onset of generalized convulsions. Our data suggest that 5-HT1A receptors play an inhibitory role in the generation of hippocampal seizures, whereas 5-HT2 receptors may participate in kindled seizure generalization from this region.
Neuroscience Letters | 1993
Yuji Wada; Mitsuhiko Nakamura; Hidehiro Hasegawa; Nariyoshi Yamaguchi
This study assessed the effects of microinjections of a serotonin (5-HT) 1A agonist, 8-OH-DPAT, into the feline hippocampus (HIP) on seizure response induced by electrical stimulation of this region. Intra-HIP injection of 8-OH-DPAT (10 nmol) produced a significant elevation in the afterdischarge threshold of partial HIP seizures, with a significant reduction in the duration of focal afterdischarge. Similarly, microinjection of 8-OH-DPAT at the same dose significantly raised the seizure threshold for eliciting generalized seizures in HIP-kindled cats. The present results demonstrate that focally applied 8-OH-DPAT possesses a potent anticonvulsant action, and provide further evidence for the inhibitory role of 5-HT1A receptors in the generation of HIP seizures.
Neuroscience Letters | 1992
Yuji Wada; Hidehiro Hasegawa; Mitsuhiko Nakamura; Nariyoshi Yamaguchi
The effects of a serotonin (5-HT) receptor agonist, 5-methoxy-N,N-dimethyltryptamine (5-MeODMT), on epileptic photosensitivity were studied in the lateral geniculate-kindled cat. 5-MeODMT at 4 mg/kg significantly suppressed photically induced myoclonus, but not paroxysmal EEG activity, at 0.5-1 h after injection. This antiepileptic effect was seen in association with the appearance of behavioral signs similar to those seen in the 5-HT syndrome. The present data provide further evidence that 5-HT plays an important role in photosensitive epilepsy, and suggest that the inhibitory effect of 5-MeODMT on photosensitivity results from its agonist action at 5-HT1 receptors.
Pharmacology, Biochemistry and Behavior | 1992
Yuji Wada; Hidehiro Hasegawa; Mitsuhiko Nakamura; Nariyoshi Yamaguchi
This study assessed the anticonvulsant effect of allopurinol (5 and 50 mg/kg, IP) on seizures kindled from the feline hippocampus. Allopurinol at a higher dose significantly reduced the behavioral seizures stage, but not afterdischarge duration, without producing any behavioral toxicity. The present results lend experimental support to the contention that allopurinol possesses anticonvulsant efficacy in the treatment of human epilepsy.
Brain & Development | 1990
Yuji Wada; Hidehiro Hasegawa; Hiroshi Okuda; Nariyoshi Yamaguchi
The acute anticonvulsant effects of zonisamide (ZNS) and phenytoin (PHT) on seizure activity produced by electrical stimulation of the feline visual cortex were studied. The intravenous administration of ZNS 60 mg/kg reduced kindled generalized seizures into partial seizures, with marked reduction in the afterdischarge duration. ZNS also suppressed focal seizure activity of the visual cortex and produced a dose-related increase in the afterdischarge threshold. The anticonvulsant effect of ZNS (60 mg/kg) was comparable to that of PHT (15 mg/kg) and was observed in the absence of neurological toxicity and background EEG changes. The present findings demonstrated that ZNS possesses potent anticonvulsant action against focal seizure and its secondary generalization from the visual cortex.
Brain Research | 1991
Yuji Wada; Hidehiro Hasegawa; Mitsuhiko Nakamura; Nariyoshi Yamaguchi
We recently demonstrated that long-lasting photosensitivity is acquired as a result of kindling of the lateral geniculate nucleus (LGN), and that the LGN-kindled cat pretreated with D, L-allylglycine represents a useful model of epilepsy for drug studies. The present experiments studied anticonvulsant effects of a serotonin precursor, L-5-hydroxytryptophan (5-HTP), on photosensitivity in the LGN-kindled cat under D,L-allylglycine and on LGN-kindled seizures. 5-HTP suppressed both myoclonic responses and paroxysmal EEG discharges induced by photic stimulation in a dose-related manner. Photically-induced seizures were completely blocked 1.5-2 h after injection of 20 mg/kg 5-HTP. 5-HTP was also effective in reducing the afterdischarge duration and behavioral seizure stage in LGN-kindled seizures; following 40 mg/kg administration, no electroclinical seizures were elicited in the LGN-kindled cats. Serotonergic mechanisms may play an important role in epileptic photosensitivity; the 5-HTP suppressive effect on photosensitivity is at least partly due to reduced neuronal activity at the level of the LGN via serotonergic inhibition.
Neuropsychobiology | 1992
Yuji Wada; Hidehiro Hasegawa; Mitsuhiko Nakamura; Nariyoshi Yamaguchi
To clarify the role of the serotonergic system in limbic and thalamic epileptic activity, we examined the effects of 5-hydroxytryptophan (5-HTP, 20 and 40 mg/kg) on fully kindled seizures from the hippocampus and lateral geniculate nucleus. The intraperitoneal administration of 20 mg/kg 5-HTP exerted no anticonvulsant effect on hippocampal kindled seizures, and a higher dose (40 mg/kg) produced a significant reduction in the behavioral seizure stage. 5-HTP at 20 mg/kg displayed no suppressive effect on lateral geniculate seizures, and 5-HTP at 40 mg/kg significantly reduced both the seizure stage and afterdischarge duration. Our data suggest that serotonergic mechanisms play an inhibitory role in seizures kindled from these brain regions.
Epilepsia | 1987
Yuji Wada; Hiroshi Okuda; Kazunori Yoshida; Hidehiro Hasegawa; Itsuki Jibiki; Hideki Kido; Nariyoshi Yamaguchi
Summary: Photosensitivity was acquired as a result of kindling in the lateral geniculate body (GL), and the GL‐kindled cat pretreated with DL‐allylglycine showed a stable level of photosensitivity. To test the usefulness as a model for the evaluation of anticonvulsant drugs, the effects of phenobarbital (PB) and phenytoin (PHT) on photosensitivity were studied in the GL‐kindled cat under DL‐allylglycine. PB (5 and 10 mg/kg intravenously, i.v.) completely suppressed photically induced seizures in most subjects at plasma concentrations of 7–16 μg/ml, and this anticonvulsant action persisted for at least 4 h after the injection. PHT (15 mg/kg, i.v.) at plasma concentrations of 9–15 μg/ml produced toxic signs, e.g., pupil dilatation, hypersalivation, and tachypnea. At this dose, PHT was inactive against photically induced myoclonus but prevented the elicitation of a generalized tonic‐clonic convulsion. From these results showing that the effects of anticonvulsant drugs on photically induced seizures can be assessed in relation to plasma concentration and acute neurologic toxicity, we suggest that the GL‐kindled cat is a potentially useful animal model of epilepsy for testing the efficacy of anticonvulsant drugs.
Pharmacology, Biochemistry and Behavior | 1992
Yuji Wada; Hidehiro Hasegawa; Mitsuhiko Nakamura; Nariyoshi Yamaguchi
This study assessed the behavioral and electrographic effects of (+)-5-methyl-10,11-dihydro-5H-dibenzo-[a,d]cyclohepten-5,10-imine maleate (MK-801) (0.1 and 0.5 mg/kg, IP), a noncompetitive antagonist of the NMDA receptors, in hippocampal (HIP)-kindled cats. MK-801 at a higher dose significantly reduced the afterdischarge duration, but not the behavioral seizure stage, of HIP-kindled seizures. This anticonvulsant effect occurred in association with the appearance of severe behavioral toxicity and paradoxical worsening of background electroencephalogram characterized by profound spike and wave discharges. The present data suggest the dissociative effect of MK-801 on seizure activity and limitations of its clinical utility as an antiepileptic agent.
Neuropsychobiology | 1992
Yuji Wada; Hidehiro Hasegawa; Mitsuhiko Nakamura; Nariyoshi Yamaguchi
This study assessed the effects of MK-801 (0.1 and 0.5 mg/kg), a noncompetitive antagonist of N-methyl-D-aspartate receptors, on focal seizure activity elicited by electrical stimulation to the feline hippocampus. Neither afterdischarge duration nor behavioral seizure stage was significantly suppressed following intraperitoneal administration of MK-801 at two dose. Rather, MK-801 at a higher dose induced hippocampal seizure status in some of the cats tested. The present data suggest convulsant properties of MK-801 and limitations of its clinical utility as an antiepileptic agent.