Serotonergic Inhibition of Limbic and Thalamic Seizures in Cats

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

doi:10.1159/000118813

Cited by 12 publications

(2 citation statements)

References 20 publications

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“…The administration of 5-HT receptor agonists or reuptake inhibitors tends to inhibit limbic and generalized seizures [142-144]. Wada et al ., (1992) recited that 5-HTP (the serotonin precursor) has a potent antiepileptic action as regards to hippocampal and lateral geniculate nucleus-kindled seizures, implying that the serotonergic system is entangled in the abolishment of epileptic activity in these brain areas [145]. In addition, patients with myoclonus had low cerebrospinal levels of 5-Hydroxyindoleacetic acid (5-HIAA; the main metabolite of serotonin) indicating that some forms of myoclonus might be pertinent to a dearth of brain serotonin [146].…”

Section: Serotoninmentioning

confidence: 99%

Estrogen and Serotonin: Complexity of Interactions and Implications for Epileptic Seizures and Epileptogenesis

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Javed

Barkat

et al. 2019

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A burgeoning literature documents the confluence of ovarian steroids and central serotonergic systems in the injuction of epileptic seizures and epileptogenesis. Estrogen administration in animals reduces neuronal death from seizures by up regulation of the prosurvival molecule i.e. Bcl-2, anti-oxidant potential and protection of NPY interneurons. Serotonin modulates epileptiform activity in either direction i.e administration of 5-HT agonists or reuptake inhibitors leads to activation of 5-HT3 and 5-HT1A receptors tending to impede focal and generalized seizures, while depletion of brain 5-HT along with destruction of serotonergic terminals leads to expanded neuronal excitability hence abatement of seizure threshold in experimental animal models. Serotonergic neurotransmission is influenced by the organizational activity of steroid hormones in growing brain and the actuation effects of steroids which come in adulthood. It is further established that ovarian steroids bring induction of dendritic spine proliferation on serotonin neurons thus thawing a profound effect on serotonergic transmission. This review features 5-HT1A and 5-HT3 receptors as potential targets for ameliorating seizure induced neurodegeneration and recurrent hypersynchronous neuronal activity. Indeed 5-HT3 receptors mediate cross talk between estrogenic and serotonergic pathways, and could well be exploited for combinatorial drug therapy against epileptogenesis.

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Section: Serotoninmentioning

confidence: 99%

Estrogen and Serotonin: Complexity of Interactions and Implications for Epileptic Seizures and Epileptogenesis

Pottoo

Javed

Barkat

et al. 2019

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“…We suggest that the release of serotonin by CBZ contributes to the therapeutic actions of CBZ. Increasing serotonin release causes anticonvulsant effects in most animal seizure models, including maximal electroshock in rats and mice (21-23), sensory-induced seizures in El mice (24), limbic and thalamic seizures in cats (25,26), audiogenic seizures in GEPRs (27-3 l), audiogenic seizures in DBA mice (32), and in seizures induced by focal injection of bicuculine into the area tempestis of the deep prepiriform cortex in rats (33,34). Depletion of brain serotonin in GEPRs decreases the anticonvulsant effectiveness of CBZ and other AEDs that release serotonin but does not alter the anticonvulsant activity of PHT, a drug that does not release serotonin (4,7).…”

Section: Fraction Numbermentioning

confidence: 99%

Carbamazepine‐Induced Release of Serotonin from Rat Hippocampus In Vitro

et al. 1998

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Summary:Purpose: Carbamazepine is one of several antiepileptic drugs (AEDs) that release the inhibitory neurotransmitter serotonin as part of their pharmacodynamic action on brain neurons. We undertook this study to investigate the cellular processes by which carbamazepine (CBZ) releases serotonin from brain tissue.Methods: Tissue slices were prepared from hippocampi of Sprague-Dawley rats. These hippocampal slices were preincubated in vitro in a buffer so that neurons within the slice would take up tritium-labeled serotonin. Subsequently the slices were superfused with buffer containing CBZ or other chemicals (or both) that increase the overflow of serotonin radioactivity.Results: Carbamazepine produced a concentration-dependent (50, 125, 250, or 500 pM) increase in basal overflow of serotonin radioactivity from superfused rat hippocampal slices in vitro. In contrast, these concentrations did not alter potassiumstimulated release, suggesting that the CBZ-induced release does not depend on depolarization or exocytosis. Blockade of the neuronal membrane serotonin transporter by fluoxetine (I FM) or citaloprarn (2 pM) did not alter overflow of serotonin radioactivity produced by 250 pM CBZ. p-chloramphetamine (10 pM) produced a substantial increase in overflow of serotonin radioactivity, and this effect appears to be antagonized by 250 FM CBZ. Uptake of ['HI-labeled serotonin into hippocampal synaptosomes was inhibited by CBZ with a median inhibitory concentration of 51 1 ? 33 pM and a Hill coefficient of 0.87 f 0.1 1, suggesting competitive inhibition of uptake by CBZ.Conclusions: We conclude that CBZ (a) releases serotonin from hippocampal slices independent of exocytosis and by a mechanism not involving the neuronal membrane serotonin transporter, and (b) at high enough concentration, blocks the neuronal serotonin transporter. Key Words: CarbamazepineSerotonin-Hippocampal slice-Anticonvulsant-Neurons.A number of antiepileptic drugs (AEDs) have been shown to increase the release or extracellular concentration of the inhibitory neurotransmitter serotonin as part of their pharmacodynamic action on neuronal tissue. This effect was demonstrated for valproate (VPA; l), zonisamide (ZNS; 2), loreclezole (LCZ), which was formerly in clinical trial in Europe (3), antiepilepsirine, a product used clinically in China (4), lamotrigine (LTG; 5), and carbamazepine (CBZ; 2,4,6,7). Unlike the aforementioned drugs, phenytoin (PHT) does not release serotonin as part of its pharmacodynamic action (7).Systemic administration of anticonvulsant doses of CBZ increases brain extracellular serotonin release, as measured by microdialysis, in intact nonepileptic rats (2,8) and in genetically epilepsy-prone rats (GEPRs; 4,6,7). The increases in extracellular serotonin are dose related (6,8), and several lines of evidence indicate that the serotonin release is integral to the mechanism by which CBZ produces its anticonvulsant effects (4,7). The CBZ-induced release can be produced by systemic (4,6, 8) as well as by focal CBZ administratio...

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Serotonin 1A receptor autoradiography during alcohol-withdrawal kindling

et al. 1997

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A series of autoradiography experiments were conducted in order to test the theory that the serotonin (5-HT) receptor subtype 5-HT(1a) is involved in alcohol-withdrawal kindled convulsive behaviour. Alcohol-withdrawal kindling was performed by subjecting male Wistar rats to multiple episodes consisting of 2 days of alcohol intoxication and 5 days of alcohol withdrawal. In the first episode alcohol intoxication led to focal downregulation of [3H]-8-hydroxy-2-(di-n-propylamino)tetralin ([3H]-8-OH-DPAT) binding sites in septum and subregions of frontal cortex, hippocampus, and entorhinal cortex. This alcohol-induced response was blunted in both alcohol-withdrawal kindled animals and in animals exposed to repeated alcohol dependence in which the previous withdrawal reactions were blocked by diazepam administration. A paradoxical upregulation of [3H]-8-OH-DPAT binding sites was found in septum and subregions of frontal cortex, hippocampus, and entorhinal cortex in control animals which were fed isocalorically with the alcohol-withdrawal kindled animals and subsequently exposed to 2 days of alcohol intoxication. It was concluded that the alterations in the alcohol induced 5-HT(1a) receptor regulation after multiple episodes of alcohol dependence were not caused by alcohol-withdrawal kindling processes per se, but were due to both alcohol specific and alcohol non-specific effects.

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Serotonergic Inhibition of Limbic and Thalamic Seizures in Cats

Cited by 12 publications

References 20 publications

Estrogen and Serotonin: Complexity of Interactions and Implications for Epileptic Seizures and Epileptogenesis

Estrogen and Serotonin: Complexity of Interactions and Implications for Epileptic Seizures and Epileptogenesis

Carbamazepine‐Induced Release of Serotonin from Rat Hippocampus In Vitro

Serotonin 1A receptor autoradiography during alcohol-withdrawal kindling

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