The 5-HT1A agonist 8-OH-DPAT increases the number of spike-wave discharges in a genetic rat model of absence epilepsy

Gerber, Katalin; Filakovszky, Janos; Halász, Péter; Bagdy, György

doi:10.1016/s0006-8993(98)00801-4

Cited by 40 publications

(23 citation statements)

References 11 publications

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“…Previous studies showed that (±)8-OH-DPAT increased the incidence of SWD in WAG/Rij rats, which was antagonized by 5-HT 1A antagonists (e.g., WAY-100635 and NAN-190) (16,17). In these animals, the 5-HT reuptake inhibitors (i.e., fluoxetine and citalopram) slightly to moderately increased the SWD generation (17).…”

mentioning

confidence: 85%

Serotonergic Modulation of Absence-Like Seizures in Groggy Rats: a Novel Rat Model of Absence Epilepsy

et al. 2010

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Abstract.To explore the role of the serotonergic system in modulating absence seizures, we examined the effects of 5-HT 1A and 5-HT 2 agonists on the incidence of spike-and-wave discharges (SWD) in Groogy (GRY) rats, a novel rat model of absence-like epilepsy. GRY rats exhibited spontaneous absence-like seizures characterized by the incidence of sudden immobile posture and synchronously-associated SWD. The total duration of SWD in GRY rats was about 300 -400 s/15-min observation period under the control conditions. However, the incidence of SWD was markedly reduced either by the 5-HT 1A agonist (±)-8-hydroxy-2-(di-n-propylamino)-tetralin [(±)8-OH-DPAT] or the 5-HT 2 agonist (±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane [(±)DOI]. The 5-HT reuptake inhibitors, fluoxetine and clomipramine, also inhibited the SWD generation. In addition, the inhibitory effects of (±)8-OH-DPAT and (±)DOI were reversed by WAY-100135 (5-HT 1A antagonist) and ritanserin (5-HT 2 antagonist), respectively. The present results suggest that the serotonergic system negatively regulates the incidence of absence seizures by stimulation of 5-HT 1A and 5-HT 2 receptors.

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confidence: 85%

Serotonergic Modulation of Absence-Like Seizures in Groggy Rats: a Novel Rat Model of Absence Epilepsy

et al. 2010

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“…There are a few studies investigating the role of serotonin (5-hydroxytryptamine, 5-HT) in absence seizures/epilepsy (Filakovszky et al, 1999;Gerber et al, 1998;Graf et al, 2004;Jakus et al, 2003;Midzyanovskaya et al, 2006;Sander et al, 2000;Sarkisova and van Luijtelaar, 2011); it has been suggested that 5HTergic neurotransmission participates in the modulation of the occurrence of SWDs in absence epilepsy through various different 5-HT receptors, by acting on the main components of the CTC loop. An increase in endogenous 5-HT produces a dual effect on SWDs; the activation of 5-HT1A receptors enhances epileptiform activity, and the activation of 5-HT2C receptors inhibits the generation of SWDs of absence epilepsy in WAG/Rij rats (Filakovszky et al, 1999;Gerber et al, 1998;Graf et al, 2004;Jakus et al, 2003).…”

Section: Serotoninmentioning

confidence: 99%

“…An increase in endogenous 5-HT produces a dual effect on SWDs; the activation of 5-HT1A receptors enhances epileptiform activity, and the activation of 5-HT2C receptors inhibits the generation of SWDs of absence epilepsy in WAG/Rij rats (Filakovszky et al, 1999;Gerber et al, 1998;Graf et al, 2004;Jakus et al, 2003).…”

Section: Serotoninmentioning

confidence: 99%

Upholding WAG/Rij rats as a model of absence epileptogenesis: Hidden mechanisms and a new theory on seizure development

Russo

Citraro

Constanti³

et al. 2016

Neuroscience & Biobehavioral Reviews

128

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Upholding WAG/Rij rats as a model of absence epileptogenesis: Hidden mechanisms and a new theory on seizure development.Neuroscience and Biobehavioral Reviews http://dx.doi.org/10. 1016/j.neubiorev.2016.09.017 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. AbstractThe WAG/Rij rat model has recently gathered attention as a suitable animal model of absence epileptogenesis. This latter term has a broad definition encompassing any possible cause that determines the development of spontaneous seizures; however, most of, if not all, preclinical knowledge on epileptogenesis is confined to the study of post-brain insult models such as traumatic brain injury or post-status epilepticus models. WAG/Rij rats, but also synapsin 2 knockout, Kv7 current-deficient mice represent the first examples of genetic models where an efficacious antiepileptogenic treatment (ethosuximide) was started before seizure onset. In this review, we have critically reconsidered all articles published regarding WAG/Rij rats, from the perspective that the period before SWD onset is considered as the latent period. In our new theory on seizure development, it is proposed that genes might be considered as the initial "insult" responsible for all plastic changes underpinning the development of spontaneous seizures. According to this idea, in WAG/Rij rats, genetic predisposition would lead to the development of abnormal bilateral cortical epileptic foci, which would then nongenetically stimulate the rest of the brain to rearrange networks in order to phenotypically develop seizures similarly to what happens during electrical kindling.

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“…1978; Buterbaugh 1978) and in WAG/Rij rats, an accepted genetic model of human absence epilepsy (Löscher and Schmidt 1988; Coenen et al . 1992; Gerber et al . 1998; Filakovszky et al .…”

Section: Brain 5‐ht Concentration and Epilepsymentioning

confidence: 99%

Serotonin and epilepsy

Bagdy

Kecskeméti

Riba

et al. 2006

Journal of Neurochemistry

Self Cite

301

216

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In recent years, there has been increasing evidence that serotonergic neurotransmission modulates a wide variety of experimentally induced seizures. Generally, agents that elevate extracellular serotonin (5-HT) levels, such as 5-hydroxytryptophan and serotonin reuptake blockers, inhibit both focal and generalized seizures, although exceptions have been described, too. Conversely, depletion of brain 5-HT lowers the threshold to audiogenically, chemically and electrically evoked convulsions. Furthermore, it has been shown that several anti-epileptic drugs increase endogenous extracellular 5-HT concentration. 5-HT receptors are expressed in almost all networks involved in epilepsies. Currently, the role of at least 5-HT 1A , 5-HT 2C , 5-HT 3 and 5-HT 7 receptor subtypes in epileptogenesis and/or propagation has been described. Mutant mice lacking 5-HT 1A or 5-HT 2C receptors show increased seizure activity and/or lower threshold. In general, hyperpolarization of glutamatergic neurons by 5-HT 1A receptors and depolarization of GABAergic neurons by 5-HT 2C receptors as well as antagonists of 5-HT 3 and 5-HT 7 receptors decrease the excitability in most, but not all, networks involved in epilepsies. Imaging data and analysis of resected tissue of epileptic patients, and studies in animal models all provide evidence that endogenous 5-HT, the activity of its receptors, and pharmaceuticals with serotonin agonist and/or antagonist properties play a significant role in the pathogenesis of epilepsies.

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The 5-HT1A agonist 8-OH-DPAT increases the number of spike-wave discharges in a genetic rat model of absence epilepsy

Cited by 40 publications

References 11 publications

Serotonergic Modulation of Absence-Like Seizures in Groggy Rats: a Novel Rat Model of Absence Epilepsy

Serotonergic Modulation of Absence-Like Seizures in Groggy Rats: a Novel Rat Model of Absence Epilepsy

Upholding WAG/Rij rats as a model of absence epileptogenesis: Hidden mechanisms and a new theory on seizure development

Serotonin and epilepsy

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