title: Effect of minocycline on pentylenetetrazol-induced chemical kindled seizures in mice.
abstract: Inflammation is one of the mechanisms involved in seizure induction. In this study, the effect of minocycline, an anti-inflammatory drug, was investigated on kindling acquisition. Chemical kindling was induced by injection of a subthreshold dose of pentylenetetrazol (PTZ; 37.5 mg/kg) in mice on every other day. Two groups of animals received minocycline (25 mg/kg) at 1 h before or 1 h after PTZ injection. Following the last PTZ injection, the changes in gene expression of TNF-α receptor, γ2 subunit of GABAA receptor and NR2A subunit of NMDA receptor were assessed in the hippocampus and piriform cortex. Injection of minocycline before PTZ increased the latency to stage 4 seizure, and decreased the duration of stages 4 and 5 seizure. It also prevented the increase in the mRNA of NR2A subunit of NMDA receptor in the hippocampus and removed the PTZ-induced increase in mRNA of γ2 subunit of GABAA receptor in piriform cortex of PTZ kindled mice. Minocycline also prevented the increase in TNF-α receptor gene expression in both hippocampus and piriform cortex. Injection of minocycline after PTZ had no significant effect on measured parameters. Therefore, it can be concluded that minocycline may exert an anticonvulsant effect through preventing the increase in GABAA and NMDA receptor subunits. These effects are accompanied by a reduction in an important inflammation index, TNF-α receptor.
authors.affiliation: Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, P.O. Box 14115-331, Tehran, Islamic Republic of Iran.
authors.forename: Nooshin
authors.initials: N
authors.lastname: Ahmadirad
authors.forename: Amir
authors.initials: A
authors.lastname: Shojaei
authors.forename: Mohammad
authors.initials: M
authors.lastname: Javan
authors.forename: Mohammad H
authors.initials: MH
authors.lastname: Pourgholami
authors.forename: Javad
authors.initials: J
authors.lastname: Mirnajafi-Zadeh
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000927:Anticonvulsants / Q000494:pharmacology*; D004195:Disease Models, Animal; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D007696:Kindling, Neurologic / Q000187:drug effects* / Q000276:immunology; D008297:Male; D051379:Mice; D008911:Minocycline / Q000494:pharmacology*; D010433:Pentylenetetrazole; D066195:Piriform Cortex / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D012333:RNA, Messenger / Q000378:metabolism; D011963:Receptors, GABA-A / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D012640:Seizures / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology
chemical_list: D000893:Anti-Inflammatory Agents; D000927:Anticonvulsants; C546280:Gabrg2 protein, mouse; C120997:NR2A NMDA receptor; D012333:RNA, Messenger; D011963:Receptors, GABA-A; D016194:Receptors, N-Methyl-D-Aspartate; D018124:Receptors, Tumor Necrosis Factor; D008911:Minocycline; D010433:Pentylenetetrazole