title: Low-frequency electrical stimulation enhances the effectiveness of phenobarbital on GABAergic currents in hippocampal slices of kindled rats.
abstract: Low frequency stimulation (LFS) has been proposed as a new approach in the treatment of epilepsy. The anticonvulsant mechanism of LFS may be through its effect on GABAA receptors, which are the main target of phenobarbital anticonvulsant action. We supposed that co-application of LFS and phenobarbital may increase the efficacy of phenobarbital. Therefore, the interaction of LFS and phenobarbital on GABAergic inhibitory post-synaptic currents (IPSCs) in kindled and control rats was investigated. Animals were kindled by electrical stimulation of basolateral amygdala in a semi rapid manner (12 stimulations/day). The effect of phenobarbital, LFS and phenobarbital+LFS was investigated on GABAA-mediated evoked and miniature IPSCs in the hippocampal brain slices in control and fully kindled animals. Phenobarbital and LFS had positive interaction on GABAergic currents. In vitro co-application of an ineffective pattern of LFS (100 pulses at afterdischarge threshold intensity) and a sub-threshold dose of phenobarbital (100μM) which had no significant effect on GABAergic currents alone, increased the amplitude and area under curve of GABAergic currents in CA1 pyramidal neurons of hippocampal slices significantly. Interestingly, the sub-threshold dose of phenobarbital potentiated the GABAergic currents when applied on the hippocampal slices of kindled animals which received LFS in vivo. Post-synaptic mechanisms may be involved in observed interactions. Obtained results implied a positive interaction between LFS and phenobarbital through GABAA currents. It may be suggested that a combined therapy of phenobarbital and LFS may be a useful manner for reinforcing the anticonvulsant action of phenobarbital.
authors.affiliation: Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
authors.forename: Azam
authors.initials: A
authors.lastname: Asgari
authors.affiliation: Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
authors.forename: Saeed
authors.initials: S
authors.lastname: Semnanian
authors.affiliation: Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran.
authors.forename: Nafiseh
authors.initials: N
authors.lastname: Atapour
authors.affiliation: Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
authors.forename: Amir
authors.initials: A
authors.lastname: Shojaei
authors.affiliation: Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
authors.forename: Homeira
authors.initials: H
authors.lastname: Moradi-Chameh
authors.affiliation: Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
authors.forename: Samireh
authors.initials: S
authors.lastname: Ghafouri
authors.affiliation: Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran.
authors.forename: Vahid
authors.initials: V
authors.lastname: Sheibani
authors.affiliation: Department of Physiology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran. Electronic address: mirnajaf@modares.ac.ir.
authors.forename: Javad
authors.initials: J
authors.lastname: Mirnajafi-Zadeh
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D056547:CA1 Region, Hippocampal / Q000187:drug effects* / Q000503:physiopathology*; D003131:Combined Modality Therapy / Q000379:methods; D004195:Disease Models, Animal; D004558:Electric Stimulation / Q000379:methods; D004599:Electric Stimulation Therapy / Q000379:methods*; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D007696:Kindling, Neurologic / Q000187:drug effects / Q000502:physiology; D008297:Male; D055369:Miniature Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D010634:Phenobarbital / Q000494:pharmacology*; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000378:metabolism; D012640:Seizures / Q000503:physiopathology / Q000628:therapy*; D046509:Tissue Culture Techniques; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D000927:Anticonvulsants; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; D010634:Phenobarbital
keywords: GABAergic currents; amygdala; hippocampus; low frequency stimulation; phenobarbital; seizure