Role of serotonin receptor subtype in seizures kindled from the feline hippocampus

Wada, Yuji; Nakamura, Mitsuhiko; Hasegawa, Hidehiro; Yamaguchi, Nariyoshi

doi:10.1016/0304-3940(92)90325-2

Cited by 65 publications

(18 citation statements)

References 22 publications

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“…Our results show that the 5-HT receptor agonist TFMPP decreases susceptibility to maximal electroconvulsions in mice and that this effect depends on stimulation of 5-HT2 or of both 5-HTlc and 5-HT, receptors, although involvement of a,adrenoceptors should also be considered. Together with data in the literature (Loscher and Czuczwar, 1985;Janusz and Kleinrok, 1989;Semenova and Ticku, 1992;Wada et al, 1992) our findings indicate that participation of a particular 5-HT receptor type or subtype in modulation of seizure susceptibility depends on the convulsive model and animal species used throughout the experiment.…”

Section: Nan-190 1-(2-methoxyphenyl)-4-[4-(2-phthalamido)butyl]pipersupporting

confidence: 74%

“…Loscher and Czuczwar (1985) showed that the anticonvulsant effect of 5-hydroxytryptophan (5-HTP) against electroconvulsions in rats is mediated by 5-HT2 receptors, whereas the proconvulsant activity of 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) in the maximal electroshock and pentylenetetrazole test in mice depends on activation of 5-HT1, receptors. However, opposite results were reported by Wada et al (1992), who examined the involvement of 5-HT1, and 5-HT2 receptors in seizures kindled from feline hippocampus. The latter investigators showed that activation of ~-H T , A receptors leads to an anticon-vulsant effect (inhibition of seizure generation), whereas stimulation of 5-HT2 receptors induces weak proconvulsant activity (increase in seizure generalization).…”

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confidence: 68%

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Role of 5‐Hydroxytryptamine Receptor Subtypes in the 1‐[3‐(Trifluoromethyl)Phenyl] Piperazine‐Induced Increase in Threshold for Maximal Electroconvulsions in Mice

1994

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The effect of 1-[3-(trifluoromethyl)phenyl] piperazine (TFMPP), a 5-hydroxytryptamine (5-HT) receptor agonist, on the threshold for maximal electroconvulsions was studied in mice. TFMPP in intraperitoneal (i.p.) doses of 10, 20 and 40 mg/kg increased the convulsive threshold (the amperage necessary to produce the hindleg tonic extensor component of seizures in 50% of animals) by 28, 60, and 85%, respectively. The effect of TFMPP (20 mg/kg) was dose-dependently blocked by 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)butyl] piperazine (NAN-190), prazosin, spiperone, mesulergine, ketanserin, and ritanserin. On the other hand, pindolol and cyanopindolol had no effect on the convulsive threshold increased by TFMPP. The results indicate that the TFMPP-induced decrease in the susceptibility to seizures is connected to stimulation of 5-HT2 or of both 5-HT1C and 5-HT2 receptors. Moreover, alpha 1-adrenoceptors also appear to be engaged in this effect.

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Section: Nan-190 1-(2-methoxyphenyl)-4-[4-(2-phthalamido)butyl]pipersupporting

confidence: 74%

mentioning

confidence: 68%

Role of 5‐Hydroxytryptamine Receptor Subtypes in the 1‐[3‐(Trifluoromethyl)Phenyl] Piperazine‐Induced Increase in Threshold for Maximal Electroconvulsions in Mice

1994

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“…Opposite results have been obtained in cats, where 8-OH-DPAt increases the AD threshold, reduces the duration of partial seizures and avoids generalized seizures induced by hippocampal kindling (Wada et al 1992(Wada et al , 1993. In agreement with this evidence, activation of 5-Ht 1A Rs reduces the EEG hippocampal epileptiform activity when induced in vitro (Salgado and Alkadhi 1995; Effects of peripheral administration of 8-OH-DPAt on pairedpulse relationship in the dentate gyrus.…”

Section: Discussionmentioning

confidence: 63%

High dose of 8-OH-DPAT decreases maximal dentate gyrus activation and facilitates granular cell plasticity in vivo

et al. 2013

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plasticity was studied. Rats injected with 8-OH-DPAt exhibited a significant reduction in MDA and epileptic discharges, a decrease in paired-pulse facilitation and an increase in long-term potentiation. this study suggests that 8-OH-DPAt or in general 5-Ht 1A/7 agonists might be useful for the treatment of tLE and also have some beneficial effects on the comorbid cognitive disorders seen in epileptic patients.

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“…For example, the 5-HT 2A -antagonist used in this study, ketanserin, protected against seizures induced by hippocampal kindling in cats (Wada et al, 1992). The same antagonist was also involved in increasing the latency to audiogenic seizures in DBA/2 mice (Semenova and Tiku, 1997).…”

Section: Discussionmentioning

confidence: 88%

Pharmacological Analysis of the Anti-epileptic Mechanisms of Fenfluramine in scn1a Mutant Zebrafish

Smolders²,

et al. 2017

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Dravet syndrome (DS) is a genetic encephalopathy that is characterized by severe seizures and prominent co-morbidities (e.g., physical, intellectual disabilities). More than 85% of the DS patients carry an SCN1A mutation (sodium channel, voltage gated, type I alpha subunit). Although numerous anti-epileptic drugs have entered the market since 1990, these drugs often fail to adequately control seizures in DS patients. Nonetheless, current clinical data shows significant seizure reduction in DS patients treated with the serotonergic (5-hydroxytryptamine, 5-HT) drug fenfluramine (FA). Recent preclinical research confirmed the anti-epileptiform activity of FA in homozygous scn1a mutant zebrafish larvae that mimic DS well. Here we explored the anti-epileptiform mechanisms of FA by investigating whether selective agonists/antagonists of specific receptor subtypes were able to counteract the FA-induced inhibition of seizures and abnormal brain discharges observed in the scn1a mutants. We show that antagonists of 5-HT1D and 5-HT2C receptor subtypes were able to do so (LY 310762 and SB 242084, respectively), but notably, a 5-HT2A-antagonist (ketanserin) was not. In addition, exploring further the mechanism of action of FA beyond its serotonergic profile, we found that the anti-epileptiform brain activity of FA was significantly abolished when it was administered in combination with a σ1-agonist (PRE 084). Our study therefore provides the first evidence of an involvement of the σ1 receptor in the mechanism of FA. We further show that the level of some neurotransmitters [i.e., dopamine and noradrenaline (NAD)] in head homogenates was altered after FA treatment, whereas γ-aminobutyric acid (GABA) and glutamate levels were not. Of interest, NAD-decreasing drugs have been employed successfully in the treatment of neurological diseases; including epilepsy and this effect could contribute to the therapeutic effect of the compound. In summary, we hypothesize that the anti-epileptiform activity of FA not only originates from its 5-HT1D- and 5-HT2C-agonism, but likely also from its ability to block σ1 receptors. These findings will help in better understanding the pharmacological profile of compounds that is critical for their applicability in the treatment of DS and possibly also other drug-resistant epilepsies.

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Role of serotonin receptor subtype in seizures kindled from the feline hippocampus

Cited by 65 publications

References 22 publications

Role of 5‐Hydroxytryptamine Receptor Subtypes in the 1‐[3‐(Trifluoromethyl)Phenyl] Piperazine‐Induced Increase in Threshold for Maximal Electroconvulsions in Mice

Role of 5‐Hydroxytryptamine Receptor Subtypes in the 1‐[3‐(Trifluoromethyl)Phenyl] Piperazine‐Induced Increase in Threshold for Maximal Electroconvulsions in Mice

High dose of 8-OH-DPAT decreases maximal dentate gyrus activation and facilitates granular cell plasticity in vivo

Pharmacological Analysis of the Anti-epileptic Mechanisms of Fenfluramine in scn1a Mutant Zebrafish

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