Neuronal Networks in Convulsant Drug-Induced Seizures
Carl L. Faingold, Gerhard H. Fromm in Drugs for Control of Epilepsy:, 2019
Thalamic nuclei are implicated as being important in the neuronal network subserving pilocarpine-induced limbic/forebrain seizures. Direct unilateral injections of bicuculline or picrotoxin into the amygdala produce recurrent seizures. Bilateral injections of GABA antagonists lead to status epilepticus, which are accompanied by histological damage in the thalamus, amygdala, olfactory cortex, SN, hippocampus, and neocortex.82 During seizures induced by a combination of lithium and pilocarpine labeling of 2-DG is increased in different brain regions, including the thalamus.83 Bilateral injections of small doses of AP7 and muscimol into the mediodorsal thalamus blocks pilocarpine-induced seizures.84 The same effect is observed with the injections of these agents in the lateral habenula.84 Systemic administration of paraoxon, an irreversible acetylcholinesterase inhibitor resulted in increased 2-DG labeling in ventral anterior nucleus of thalamus as well as external globus pallidus, entopeduncular nucleus, and SNR.85
Phytotherapeutic Agents in Epilepsy
Vikas Kumar, Addepalli Veeranjaneyulu in Herbs for Diabetes and Neurological Disease Management, 2018
The quest for improved antiepileptic agents depends on the quality of reliable epileptic models of epilepsy which should throw light on their mechanism of action also. Several animal models have been utilized in the search of more efficacious and safer antiepileptic agents. Established animal models include leptazole-induced seizures, maximal electroshock seizure (MES), picrotoxin (PIC)-induced convulsions, metrazole-induced seizures (MIS), pilocarpine (PIL)-, pentylenetetrazol (PTZ)-, kainite (KA)-, and strychnine (STR)-induced seizures. These models are employed in the early phase of antiepileptic drug discovery and are highly predictive of concomitant efficacy in generalized and partial epilepsy.13 The most commonly employed animal models are the MES test, PTZ seizure test, and PIC-induced convulsions.14,15 The MES and PTZ seizure models continue to be the most widely used animal seizure models in this regard.16 The drugs clinically active against spike-wave seizures (e.g., valproic acid, ethosuximide, trimethadione, and BZD) block the PTZ-induced clonic seizures.13 Thus, positive results in the PTZ seizure test are considered to be suggestive of potential clinical utility against generalized absence epilepsy. These tests have been used to establish the efficacy of the plants which have been traditionally known for their anticonvulsant activity. Various animal model studies have been conducted with plant extracts or active constituents isolated from the plants.
Synthesis, Enzyme Localization, and Regulation of Neurosteroids
Sheryl S. Smith in Neurosteroid Effects in the Central Nervous System, 2003
355-360, 1987. Majewska, M.D., Demirgoren, S., and London, E.D., Binding of pregnenolone sulfate to rat brain membranes suggests multiple sites of steroid action at the GABAA receptor, Eur. J. Pharmacol., 189, 307-315, 1990.Gee, K.W., Joy, D.S., and Belelli, D., Complex interactions between pregnenolone sulfate and the t-butylbicyclophosphorothionate-labeled chloride ionophore in rat brain, Brain Res., 482, 169-173, 1989.Yoon, K.W., Covey, D.F., and Rothman, S.M., Multiple mechanisms of picrotoxin block of GABA-induced currents in rat hippocampal neurons, J. Physiol., 464,
Moringa oleifera seed ethanol extract and its active component kaempferol potentiate pentobarbital-induced sleeping behaviours in mice via a GABAergic mechanism
Published in Pharmaceutical Biology, 2022
Wei-Liang Liu, Bai-Fen Wu, Jian-Hua Shang, Xue-Feng Wang, Yun-Li Zhao, Ai-Xiang Huang
Pentobarbital sodium (PENT), flumazenil (FMZ), muscimol (MUS), bicuculline (BIC), sodium carboxymethyl cellulose (CMC-Na), polyoxyethylene sorbitan monooleate (Tween-80, TW) and picrotoxin (PIC) were purchased from Sigma-Aldrich Chemical Inc. (St. Louis, MO, USA). Pentylenetetrazole (PTZ) was obtained from National Institute for Food and Drug Control (Beijing, China), and estazolam tablets (EST) were bought from Huazhong Pharmaceutical Inc. (Wuhan, Hubei, China). Mouse γ-amino butyric acid (GABA) and glutamic (Glu) ELISA kit were purchased from Jiancheng Biotech Inc. (Nanjing, China). KA (≥95%) was purchased from Coolaber Biotech Inc. (Beijing, China). Specific rabbit polyclonal antibodies against GABAA receptors subunits (α1, γ2) or glutamate decarboxylase (GAD65/67) and the corresponding conjugated antirabbit immunoglobulin G-horseradish peroxidase were obtained from Abcam Inc. (Cambridge, UK). Human cerebellar granule cells (HCGC) were purchased from the BeNa Culture Collection Inc. (Beijing, China). Dulbecco’s Modified Eagle’s Medium (DMEM) and foetal bovine serum (FBS) were purchased from GIBCO Inc. (Grand Island, NY, USA). The Cl--sensitive fluorescence probe (SFLUOP) and N-(ethoxycarbonylmethyl)-6-methoxyquinolinium bromide (MQAE) were obtained from Invitrogen Inc. (Carlsbad, CA, USA). All other chemical agents used in the study were of analytical grade.
Loss of mGluR1-LTD following cocaine exposure accumulates Ca2+-permeable AMPA receptors and facilitates synaptic potentiation in the prefrontal cortex
Published in Journal of Neurogenetics, 2021
The following drugs were used: cocaine (Sigma-Aldrich), (S)-3,5-Dihydroxyphenylglycine (DHPG, Tocris Bioscience), LY367385 (Tocris Bioscience), 3-((2-Methyl-1,3-thiazol-4-yl)ethynyl)pyridine hydrochloride (MTEP, Tocris Bioscience), 1-Naphthyl acetyl spermine trihydrochloride (Naspm, Sigma-Aldrich), picrotoxin (Sigma-Aldrich), PKI6-22 (Sigma-Aldrich), QX-314 (Sigma-Aldrich), rapamycin (Sigma-Aldrich), Ro67-7476 (Tocris Bioscience), SCH23390 (Tocris Bioscience), SKF81297 (Sigma-Aldrich), tetrodotoxin (Sigma-Aldrich), and U73122 (Tocris Bioscience). Picrotoxin was dissolved directly in the ACSF used for perfusion. LY367385 and MTEP were dissolved in DMSO with a 1:1000 ratio as stock solutions, which were added directly to ASCF to a desired final concentration during experiments. All other drugs were dissolved in distilled water with a 1:1000 ratio as stock solutions. Drugs were delivered to the recording chamber through a perfusion system (Harvard Apparatus).
Ultrastructural GABA immunogold labeling in the substantia nigra pars reticulata of kindled genetic absence epilepsy rats
Published in Ultrastructural Pathology, 2020
Serap Sirvanci, Dilek Akakin, Medine Gulcebi İdrizoglu, Ozlem Tugce Kaya, Tugba Karamahmutoglu, Zehra Nur Turgan Aşık, Filiz Onat
Mechanisms of stopping an absence seizure involve superficial and intermediate layers of superior colliculus, as well as the excitatory projections from the superior colliculus to the thalamus.26–28 Also, direct and indirect pathways from the basal ganglia generate disinhibition in the superior colliculus, resulting in the suppression of absence seizures.26–29 The nigro-thalamo-cortical pathway and the pedunculopontine tegmental nucleus are also involved in controlling absence seizures.14,26 In a previous study, GABA-releasing polymer matrices were grafted into the SN in the amygdala kindling model and the seizures were repressed.30 Transplantation of fetal GABAergic cells, immortalized GABAergic cells, or transgenic cell lines into the SN were reported to suppress the seizures in the kindling, pilocarpine, and kainic acid models.26,31–33 Decreasing the activity of the SNR leads to disinhibition of the output structures of the SNR, such as the superior colliculus and the ventromedial thalamus, resulting in the suppression of seizures.12,14 In contrast, application of picrotoxin, a GABAA receptor antagonist, to the SNR leads to the development of absence seizures.13
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