title: Epileptiform response of CA1 neurones to convulsant stimulation by cyclothiazide, kainic acid and pentylenetetrazol in anaesthetized rats.
abstract: We have previously reported that cyclothiazide (CTZ) evokes epileptiform activities in hippocampal neurons and induces seizure behavior. Here we further studied in vivo the sensitivity of the hippocampal CA1 neurons in response to CTZ in epileptogenesis in comparison with two other classic convulsants of kainic acid (KA) and pentylenetetrazol (PTZ). CTZ administered intracerebral ventricle (i.c.v.) induced epileptiform activities from an initial of multiple evoked population spikes, progressed to spontaneous spikes and finally to highly synchronized burst activities in hippocampal CA1 neurons. PTZ, when given by subcutaneously, but not by intracerebral ventricle injection, evoked similar progressive epileptiform activities. In contrast, KA given by i.c.v. induced a quick development of epileptiform burst activities and then shortly switched to continuous high frequency firing as acute status epilepticus (ASE). Pharmacologically, alprazolam, a high-potency benzodiazepine ligand, inhibited CTZ and PTZ, but not KA, induced epileptiform burst activities while GYKI 53784, an AMPA receptor antagonist, suppressed CTZ and KA but not PTZ evoked epileptiform activities. In conclusion, CTZ and PTZ induced epileptiform activities are most likely to share a similar progressive pattern in hippocampus with GABAergic mechanism dominant in epileptogenesis, while CTZ model involves additional glutamate receptor activation. KA induced seizure in hippocampus is different to that of both CTA and PTZ. The results from this study indicate that hippocampal neurons respond to various convulsant stimulation differently which may reflect the complicated causes of the seizure in clinics.
authors.affiliation: Institutes of Brain Science, State Key Laboratory for Medical Neurobiology, Fudan University, Shanghai 200032, China.
authors.forename: Binbin
authors.initials: B
authors.lastname: Qian
authors.forename: Yajie
authors.initials: Y
authors.lastname: Sun
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wu
authors.forename: Li
authors.initials: L
authors.lastname: Wan
authors.forename: Lulan
authors.initials: L
authors.lastname: Chen
authors.forename: Shuzhen
authors.initials: S
authors.lastname: Kong
authors.forename: Binhong
authors.initials: B
authors.lastname: Zhang
authors.forename: Fayong
authors.initials: F
authors.lastname: Zhang
authors.forename: Zhen-Yu
authors.initials: ZY
authors.lastname: Wang
authors.forename: Yun
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D001581:Benzothiadiazines / Q000008:administration & dosage*; D003292:Convulsants / Q000008:administration & dosage*; D004594:Electrophysiology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects*; D007276:Injections, Intraventricular; D007608:Kainic Acid / Q000008:administration & dosage*; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D010433:Pentylenetetrazole / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology
chemical_list: D001581:Benzothiadiazines; D003292:Convulsants; C004639:cyclothiazide; D007608:Kainic Acid; D010433:Pentylenetetrazole